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| Speech apraxia v1.0 | KDM5C |
Thomas Scerri changed review comment from: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209). Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though. Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes. Sources: Expert list, Expert Review; to: First reported CAS case with a de novo KDM5C frameshift variant (Kaspi et al., 2022; PMID: 36117209). Leonardi et al. (2023; PMID: 36434256) report 30 individuals with KDM5C variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though. Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes. Sources: Expert list, Expert Review |
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| Speech apraxia v1.0 | SETD1A | Thomas Scerri edited their review of gene: SETD1A: Changed rating: GREEN; Changed publications: 29463886, 32346159, 36117209 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v1.0 | SETD1A |
Thomas Scerri changed review comment from: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886) Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886) Kaspi et al. (2022; PMID: 36117209) report a CAS proband with a de novo SETD1A splice acceptor variant. An independent (unpublished) in-house CAS proband has a de novo SETD1A frameshift variant. Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1). Sources: Expert list, Expert Review |
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| Speech apraxia v1.0 | Zornitza Stark promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.39 | KAT6A |
Thomas Scerri changed review comment from: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886). Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia. St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. " Sources: Expert list, Expert Review; to: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886). Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature. St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. " Sources: Expert list, Expert Review |
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| Speech apraxia v0.39 | Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | FOXP2 |
Thomas Scerri changed review comment from: Additional phenotypes: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112).; to: Lai et al. (2001; PMID: 11586359) reported a 3-generation family with speech apraxia carrying a missense FOXP2 variant and also an independent case with a translocation affecting FOXP2. Morison et al. (2023; PMID 36328423) "phenotyped 28 individuals from 17 families with pathogenic FOXP2-only variants (12 loss-of-function, five missense variants; 14 males; aged 2 to 62 years)" and found "speech disorders were prevalent (23/25, 92%) and CAS was most common (22/25, 88%)". |
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| Speech apraxia v0.38 | KDM5C |
Thomas Scerri changed review comment from: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209). Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though. Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes. Sources: Expert list, Expert Review; to: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209). Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of speech/verbal apraxia or dyspraxia though. Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | ZBTB18 |
Thomas Scerri changed review comment from: First reported CAS case with an de novo nonsense ZBTB18 variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review; to: First reported CAS case with an de novo ZBTB18 nonsense variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | TAOK2 |
Thomas Scerri changed review comment from: First reported CAS case with an de novo missense TAOK2 variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review; to: First reported CAS case with an de novo TAOK2 missense variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | SPAST |
Thomas Scerri changed review comment from: First reported CAS case with an de novo missense SPAST variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review; to: First reported CAS case with an de novo SPAST missense variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | PURA |
Thomas Scerri changed review comment from: First reported CAS case with an inherited PURA missense variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected. Sources: Expert list, Expert Review; to: First reported CAS case with an inherited PURA missense variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected. Also several cases of "absence of speech" in the literature. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | PURA |
Thomas Scerri changed review comment from: First reported CAS case with an inherited missense PURA variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected. Sources: Expert list, Expert Review; to: First reported CAS case with an inherited PURA missense variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | PHF21A |
Thomas Scerri changed review comment from: First reported CAS case with a de novo frameshift PHF21A variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo PHF21A frameshift variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | KDM5C |
Thomas Scerri changed review comment from: First reported CAS case with a de novo frameshift HNRNPK variant (Kaspi et al., 2022; PMID: 36117209). Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though. Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes. Sources: Expert list, Expert Review; to: First reported CAS case with a de novo HNRNPK frameshift variant (Kaspi et al., 2022; PMID: 36117209). Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though. Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | SHANK3 |
Thomas Scerri changed review comment from: First reported CAS case with an de novo frameshift SHANK3 variant (Kaspi et al., 2022; PMID: 36117209). Brignell et al. (2021; PMID: 33293697) report 2 cases of CAS in a cohort of individuals with Phelan-McDermid/22q13 deletion syndrome, caused by heterozygous loss of function of SHANK3. Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SHANK3 frameshift variant (Kaspi et al., 2022; PMID: 36117209). Brignell et al. (2021; PMID: 33293697) report 2 cases of CAS in a cohort of individuals with Phelan-McDermid/22q13 deletion syndrome, caused by heterozygous loss of function of SHANK3. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | CHD3 |
Thomas Scerri changed review comment from: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886). Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia. Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia.; to: First reported CAS case with a de novo CHD3 missense variant (Eising et al., 2019; PMID: 29463886). Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia. Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia. |
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| Speech apraxia v0.38 | TNRC6B | Thomas Scerri edited their review of gene: TNRC6B: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | TNRC6B |
Thomas Scerri changed review comment from: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886) These additional supporting studies are for speech delay rather than speech apraxia per se: Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B. Yang et al. (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B. Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886) These additional supporting studies are for speech delay rather than speech apraxia per se: Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a loss-of-function variant in TNRC6B. Yang et al. (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying loss-of-function variants in TNRC6B. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | MKL2 | Thomas Scerri edited their review of gene: MKL2: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | GNAO1 | Thomas Scerri edited their review of gene: GNAO1: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | ERF | Thomas Scerri edited their review of gene: ERF: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | SHANK3 | Thomas Scerri edited their review of gene: SHANK3: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | ZNF142 |
Thomas Scerri changed review comment from: A reported CAS proband with compound heterozygous missenses ZNF142 variants (Hildebrand et al., 2020; PMID: 32345733). Khan et al. (2019, PMID: 31036918) report 7 cases with compound heterozygous or else homozygous LoF or missense ZNF142 variants for which the cases have a range of speech deficits including speech apraxia in one case. Kameyama et al. (2020, PMID: 34531528) report two brothers with biallelic LoF ZNF142 variants for which the cases have speech deficits. Christensen et al. (2022; PMID: 35616059) report a further 26 individuals with biallelic ZNF142 variants for which the cases have a range of speech deficits. Sources: Expert list, Expert Review; to: First reported CAS proband with compound heterozygous ZNF142 missenses variants (Hildebrand et al., 2020; PMID: 32345733). Khan et al. (2019, PMID: 31036918) report 7 cases with compound heterozygous or else homozygous loss-of-function or missense ZNF142 variants for which the cases have a range of speech deficits, including speech apraxia in one case. Kameyama et al. (2020, PMID: 34531528) report two brothers with biallelic loss-of-function ZNF142 variants for which the cases have speech deficits. Christensen et al. (2022; PMID: 35616059) report a further 26 individuals with biallelic ZNF142 variants for which the cases have a range of speech deficits. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | UPF2 |
Thomas Scerri changed review comment from: A CAS proband with a de novo LoF UPF2 variant (Hildebrand et al., 2020; PMID: 32345733). Johnson et al. (2019; PMID: 31585809) report 3 independent cases with LoF UPF2 variants and a range of speech deficits, including speech apraxia in one of the cases (although the speech disorder had resolved to a mild phonological disorder at later testing). Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo UPF2 frameshift variant (Hildebrand et al., 2020; PMID: 32345733). Johnson et al. (2019; PMID: 31585809) report 3 independent cases with loss-of-function UPF2 variants and a range of speech deficits, including speech apraxia in one of the cases (although the speech disorder had resolved to a mild phonological disorder at later testing). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | POGZ |
Thomas Scerri changed review comment from: Only reported CAS proband with a de novo missense POGZ variant (Hildebrand et al., 2020; PMID: 32345733). Nagy et al. (2022; PMID: 35052493) reported 117 cases from a meta-analysis and found that "the most common symptoms were speech delay in 88%". This is not strong enough evidence to be supporting evidence for speech apraxia per se. Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo POGZ missense variant (Hildebrand et al., 2020; PMID: 32345733). Nagy et al. (2022; PMID: 35052493) reported 117 cases from a meta-analysis and found that "the most common symptoms were speech delay in 88%". This is not strong enough evidence to be supporting evidence for speech apraxia per se. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | MEIS2 |
Thomas Scerri changed review comment from: First reported CAS proband with a LoF MEI2 variant (Hildebrand et al., 2020; PMID: 32345733). Douglas et al. (2018; PMID: 30055086) report 3 new cases with de novo missense variants and 2 previously published deletion and nonsense variants. All cases have a range of differently worded speech problems, and one has verbal apraxia. Sources: Expert Review, Expert list; to: First reported CAS proband with a MEI2 frameshift variant (Hildebrand et al., 2020; PMID: 32345733). Douglas et al. (2018; PMID: 30055086) report 3 new cases with de novo missense variants and 2 previously published deletion and nonsense variants. All cases have a range of differently worded speech problems, and one has verbal apraxia. Sources: Expert Review, Expert list |
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| Speech apraxia v0.38 | GNB1 |
Thomas Scerri changed review comment from: Only reported CAS proband with a de novo nonsense GNB1 variant (Hildebrand et al., 2020; PMID: 32345733). Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo GNB1 nonsense variant (Hildebrand et al., 2020; PMID: 32345733). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | GNAO1 |
Thomas Scerri changed review comment from: First reported CAS proband with a de novo missense GNAO1 variant (Hildebrand et al., 2020; PMID: 32345733). These additional cases are less clear for speech apraxia: Wirth et al. (2020; PMID: 35722775) reported twenty-four independent cases with a range of de novo and inherited variants, including missense and nonsense, for which a speech disorder (dysarthria) was reported for 19 individuals. Lasa-Aranzasti et al. (2024; PMID: 38881224) report eighteen independent cases and find "all patients developed some type of nonverbal communication, but only four acquired verbal language." Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo GNAO1 missense variant (Hildebrand et al., 2020; PMID: 32345733). These additional cases are less clear for speech apraxia: Wirth et al. (2020; PMID: 35722775) reported twenty-four independent cases with a range of de novo and inherited variants, including missense and nonsense, for which a speech disorder (dysarthria) was reported for 19 individuals. Lasa-Aranzasti et al. (2024; PMID: 38881224) report eighteen independent cases and find "all patients developed some type of nonverbal communication, but only four acquired verbal language." Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | EBF3 |
Thomas Scerri changed review comment from: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically had apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases had "expressive speech disorder (3/3)" and one was reported with apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | EBF3 |
Thomas Scerri changed review comment from: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically has apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically had apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | EBF3 |
Thomas Scerri changed review comment from: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and one specifically has apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | EBF3 | Thomas Scerri edited their review of gene: EBF3: Changed publications: 32345733, 28017372, 35340043 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | EBF3 |
Thomas Scerri changed review comment from: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Of these ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo EBF3 nonsense variant (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Specifically, of these ten cases, carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | DDX3X |
Thomas Scerri changed review comment from: First reported CAS proband with a de novo LoF DDX3X variant (Hildebrand et al., 2020; PMID: 32345733). Second reported CAS proband with a de novo LoF DDX3X variant (Kaspi et al., 2022; PMID: 36117209) Third in-house CAS proband with a de novo LoF DDX3X variant (not published). Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)". Sources: Expert list, Expert Review; to: Hildebrand et al. (2020; PMID: 32345733) report the first CAS case has a de novo DDX3X frameshift variant. Kaspi et al. (2022; PMID: 36117209) report a case with dysarthria and a de novo DDX3X nonsense variant. An independent (unpublished) in-house CAS proband has a de novo DDX3X nonsense variant. Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%; 30/34)". Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | CDK13 |
Thomas Scerri changed review comment from: First proband with a de novo missense CDK13 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733). Morison et al. (2023; PMID: 36599938) report 41 cases (with 33 novel variants) and find "most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22)." Sources: Expert list, Expert Review; to: First reported CAS case with a de novo CDK13 missense variant (Hildebrand et al., 2020; PMID: 32345733). Morison et al. (2023; PMID: 36599938) report 41 cases (with 33 novel variants) and find "most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22)." Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | ERF |
Thomas Scerri changed review comment from: First two reported CAS cases with a ERF nonsense variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband. Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder. Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments. Sources: Expert list, Expert Review; to: First two reported CAS cases with a ERF nonsense variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband. Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder. Moddemann et al. (2022; PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | ERF |
Thomas Scerri changed review comment from: First two reported CAS cases with a nonsense ERF variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband. Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder. Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments. Sources: Expert list, Expert Review; to: First two reported CAS cases with a ERF nonsense variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband. Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder. Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | DIP2C |
Thomas Scerri changed review comment from: First reported CAS proband with a de novo splice DIP2C variant (Kaspi et al., 2022; PMID: 36117209). Ha et al. (2024; PMID: 38421105) report 23 cases with various DIP2C variants, including the one published by Kaspi et al. (2022; PMID: 36117209). All 23 cases have various speech deficits and two (including the Kaspi et al. (2022) case) are reported having speech apraxia. Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo DIP2C splice acceptor variant (Kaspi et al., 2022; PMID: 36117209). Ha et al. (2024; PMID: 38421105) report 23 cases with various DIP2C variants, including the one published by Kaspi et al. (2022; PMID: 36117209). All 23 cases have various speech deficits and two (including the Kaspi et al. (2022) case) are reported having speech apraxia. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | BRPF1 |
Thomas Scerri changed review comment from: First reported CAS proband with a de novo missense BRPF1 variant (Kaspi et al., 2022; PMID: 36117209). Yan et al. (2017; PMID: 27939640) reported 10 independent cases with de novo or inherited BRPF1 variants and with a range of speech and language deficits, including one proband with speech apraxia (proband 4, Table S1). Morison et al. (2024; PMID: 38346666) report 15 new cases with mostly de novo BRPF1 variants and a range of speech deficits, including 3 specifically with speech apraxia. Sources: Expert list, Expert Review; to: First reported CAS case with a de novo BRPF1 missense variant (Kaspi et al., 2022; PMID: 36117209). Yan et al. (2017; PMID: 27939640) reported 10 independent cases with de novo or inherited BRPF1 variants and with a range of speech and language deficits, including one proband with speech apraxia (proband 4, Table S1). Morison et al. (2024; PMID: 38346666) report 15 new cases with mostly de novo BRPF1 variants and a range of speech deficits, including 3 specifically with speech apraxia. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | ARHGEF9 |
Thomas Scerri changed review comment from: Only reported CAS proband with a de novo nonsense ARHGEF9 variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo ARHGEF9 nonsense variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | ZFHX4 |
Thomas Scerri changed review comment from: First proband with splice acceptor ZFHX4 variant reported for CAS (Eising et al., 2019; PMID: 29463886). Fontana et al. (2021; PMID: 34461323) report a similar splice region variant in ZFHX4 for a proband with a neuropsychological phenotype, and summarise other probands with deletions or point mutations and associated phenotypes. Only one of these has a recorded speech phenotype. Overall this paper doesn't add strong evidence for a link between speech apraxia and ZFHX4. Sources: Expert list, Expert Review; to: First reported CAS case with a ZFHX4 splice acceptor variant (Eising et al., 2019; PMID: 29463886) Fontana et al. (2021; PMID: 34461323) report a similar splice region variant in ZFHX4 for a proband with a neuropsychological phenotype, and summarise other probands with deletions or point mutations and associated phenotypes. Only one of these has a recorded speech phenotype. Overall this paper doesn't add strong evidence for a link between speech apraxia and ZFHX4. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | WDR5 |
Thomas Scerri changed review comment from: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886) Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." However, only 1 was diagnosed with speech dyspraxia. Sources: Expert list, Expert Review; to: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886) Snijders Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." However, only 1 was diagnosed with speech dyspraxia. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | WDR5 | Thomas Scerri edited their review of gene: WDR5: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | WDR5 |
Thomas Scerri changed review comment from: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886) Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." Sources: Expert list, Expert Review; to: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886) Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." However, only 1 was diagnosed with speech dyspraxia. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | TNRC6B |
Thomas Scerri changed review comment from: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886) These additional supporting studies are for speech delay rather than speech apraxia per se: Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B. Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B. Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886) These additional supporting studies are for speech delay rather than speech apraxia per se: Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B. Yang et al. (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | TNRC6B |
Thomas Scerri changed review comment from: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886) These additional supporting studies are for speech delay rather than speech apraxia per se: Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B. Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B. Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886) These additional supporting studies are for speech delay rather than speech apraxia per se: Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al. (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B. Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | WDR5 |
Thomas Scerri changed review comment from: First proband with a de novo missense WDR5 variant reported for CAS (Eising et al., 2019; PMID: 29463886). Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." Sources: Expert list, Expert Review; to: First reported CAS case with a de novo WDR5 missense variant (Eising et al., 2019; PMID: 29463886) Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | TNRC6B |
Thomas Scerri changed review comment from: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886). These additional supporting studies are for speech delay rather than speech apraxia per se: Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B. Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B. Sources: Expert list, Expert Review; to: First reported CAS case with a TNRC6B nonsense variant (Eising et al., 2019; PMID: 29463886) These additional supporting studies are for speech delay rather than speech apraxia per se: Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B. Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B. Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | SETD1A |
Thomas Scerri changed review comment from: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886). Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886) Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | SETD1B |
Thomas Scerri changed review comment from: First reported CAS case with a de novo missense SETD1B variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1B missense variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | SETBP1 |
Thomas Scerri changed review comment from: First proband with LoF SETBP1 variant reported for CAS (Eising et al., 2019; PMID: 29463886) Thirty one further probands with LoF SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%) being the most common diagnosis.". Sources: Expert list, Expert Review; to: First reported CAS case with a SETBP1 frameshift variant reported for CAS (Eising et al., 2019; PMID: 29463886) Thirty one further probands with loss-of-function SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%; 25/31) being the most common diagnosis.". Sources: Expert list, Expert Review |
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| Speech apraxia v0.38 | ZBTB18 | Zornitza Stark Marked gene: ZBTB18 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | ZBTB18 | Zornitza Stark Gene: zbtb18 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | ZBTB18 | Zornitza Stark Classified gene: ZBTB18 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.38 | ZBTB18 | Zornitza Stark Gene: zbtb18 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.37 | TRIP12 | Zornitza Stark Marked gene: TRIP12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.37 | TRIP12 | Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.37 | TRIP12 | Zornitza Stark Classified gene: TRIP12 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.37 | TRIP12 | Zornitza Stark Gene: trip12 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.36 | TAOK2 | Zornitza Stark Marked gene: TAOK2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.36 | TAOK2 | Zornitza Stark Gene: taok2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.36 | TAOK2 | Zornitza Stark Classified gene: TAOK2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.36 | TAOK2 | Zornitza Stark Gene: taok2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.35 | SPAST | Zornitza Stark Marked gene: SPAST as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.35 | SPAST | Zornitza Stark Gene: spast has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.35 | SPAST | Zornitza Stark Classified gene: SPAST as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.35 | SPAST | Zornitza Stark Gene: spast has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.34 | SHANK3 | Zornitza Stark Marked gene: SHANK3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.34 | SHANK3 | Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.34 | SHANK3 | Zornitza Stark Classified gene: SHANK3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.34 | SHANK3 | Zornitza Stark Gene: shank3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.33 | SETD1B | Zornitza Stark Marked gene: SETD1B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.33 | SETD1B | Zornitza Stark Gene: setd1b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.33 | SETD1B | Zornitza Stark Classified gene: SETD1B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.33 | SETD1B | Zornitza Stark Gene: setd1b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.32 | RBFOX3 | Zornitza Stark Marked gene: RBFOX3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.32 | RBFOX3 | Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.32 | RBFOX3 | Zornitza Stark Classified gene: RBFOX3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.32 | RBFOX3 | Zornitza Stark Gene: rbfox3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.31 | MKL2 |
Thomas Scerri changed review comment from: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023). Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112). Sources: Expert list, Expert Review; to: First reported CAS case with a MKL2 splice acceptor variant (Eising et al., 2019; PMID: 29463886). However, it is only predicted to be likely pathogenic and is observed 500+ times in gnomad v4 and has a low variant quality score. Andrews et al. (2023; PMID: 37013900) identify two cases with de novo MKL2 missense variants (p.R104G and p.A91P) with reported gain of function. One case is reported with apraxia and the other with speech apraxia (Table 1). Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112). Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | KAT6A |
Thomas Scerri changed review comment from: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886). Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with CHD3 variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia. St John et al. (2022; PMID: 35892268) examined 49 cases and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. " Sources: Expert list, Expert Review; to: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886). Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia. St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. " Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | KAT6A |
Thomas Scerri changed review comment from: Additional phenotypes: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886). Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with CHD3 variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia. St John et al. (2022; PMID: 35892268) examined 49 cases and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. " Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | CHD3 |
Thomas Scerri changed review comment from: Additional phenotypes: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).; to: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886). Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia. Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia. |
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| Speech apraxia v0.31 | ZBTB18 |
Thomas Scerri gene: ZBTB18 was added gene: ZBTB18 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: ZBTB18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZBTB18 were set to 36117209 Phenotypes for gene: ZBTB18 were set to Intellectual developmental disorder, autosomal dominant 22, MIM# 612337 Review for gene: ZBTB18 was set to RED Added comment: First reported CAS case with an de novo nonsense ZBTB18 variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | TRIP12 |
Thomas Scerri gene: TRIP12 was added gene: TRIP12 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: TRIP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRIP12 were set to 36117209 Phenotypes for gene: TRIP12 were set to Intellectual developmental disorder, autosomal dominant 49, MIM# 617752 Review for gene: TRIP12 was set to RED Added comment: First reported CAS case with a de novo exon duplication of TRIP12 (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | TAOK2 |
Thomas Scerri gene: TAOK2 was added gene: TAOK2 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: TAOK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TAOK2 were set to 36117209 Phenotypes for gene: TAOK2 were set to Neurodevelopmental disorder (MONDO:0700092), TAOK2-related Review for gene: TAOK2 was set to RED Added comment: First reported CAS case with an de novo missense TAOK2 variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | SPAST |
Thomas Scerri gene: SPAST was added gene: SPAST was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPAST were set to 36117209 Phenotypes for gene: SPAST were set to Spastic paraplegia 4, autosomal dominant, MIM# 182601 Review for gene: SPAST was set to RED Added comment: First reported CAS case with an de novo missense SPAST variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | SHANK3 |
Thomas Scerri gene: SHANK3 was added gene: SHANK3 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SHANK3 were set to 36117209; 33293697 Phenotypes for gene: SHANK3 were set to Phelan-McDermid syndrome, MIM# 606232 Review for gene: SHANK3 was set to GREEN Added comment: First reported CAS case with an de novo frameshift SHANK3 variant (Kaspi et al., 2022; PMID: 36117209). Brignell et al. (2021; PMID: 33293697) report 2 cases of CAS in a cohort of individuals with Phelan-McDermid/22q13 deletion syndrome, caused by heterozygous loss of function of SHANK3. Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | SETD1B |
Thomas Scerri gene: SETD1B was added gene: SETD1B was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: SETD1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SETD1B were set to 36117209 Phenotypes for gene: SETD1B were set to Intellectual developmental disorder with seizures and language delay, MIM# 619000 Review for gene: SETD1B was set to RED Added comment: First reported CAS case with a de novo missense SETD1B variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | RBFOX3 |
Thomas Scerri gene: RBFOX3 was added gene: RBFOX3 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: RBFOX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RBFOX3 were set to 36117209; 24039908 Phenotypes for gene: RBFOX3 were set to Neurodevelopmental disorder (MONDO:0700092), RBFOX3-related Review for gene: RBFOX3 was set to AMBER Added comment: First reported CAS case with a paternally inherited nonsense RBFOX3 variant (Kaspi et al., 2022; PMID: 36117209). The carrier father was also affected. Lal et al. (2013; PMID: 24039908) report two cases with nonsense RBFOX3 variants, both with initial speech or language delay, and one of which with "Moderate developmetal delay, delayed speech development, mild oral dyspraxia". Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | HNRNPK | Zornitza Stark Marked gene: HNRNPK as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.31 | HNRNPK | Zornitza Stark Gene: hnrnpk has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.31 | HNRNPK | Zornitza Stark Classified gene: HNRNPK as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.31 | HNRNPK | Zornitza Stark Gene: hnrnpk has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.30 | KDM5C | Zornitza Stark Marked gene: KDM5C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.30 | KDM5C | Zornitza Stark Gene: kdm5c has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.30 | KDM5C | Zornitza Stark Classified gene: KDM5C as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.30 | KDM5C | Zornitza Stark Gene: kdm5c has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.29 | PHF21A | Zornitza Stark Marked gene: PHF21A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.29 | PHF21A | Zornitza Stark Gene: phf21a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.29 | PHF21A | Zornitza Stark Classified gene: PHF21A as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.29 | PHF21A | Zornitza Stark Gene: phf21a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.28 | PURA | Zornitza Stark Marked gene: PURA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.28 | PURA | Zornitza Stark Gene: pura has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.28 | PURA | Zornitza Stark Classified gene: PURA as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.28 | PURA | Zornitza Stark Gene: pura has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.27 | PURA | Thomas Scerri edited their review of gene: PURA: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.27 | PURA |
Thomas Scerri gene: PURA was added gene: PURA was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: PURA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PURA were set to 36117209 Phenotypes for gene: PURA were set to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties, MIM# 616158 Added comment: First reported CAS case with an inherited missense PURA variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected. Sources: Expert list, Expert Review |
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| Speech apraxia v0.27 | PHF21A |
Thomas Scerri gene: PHF21A was added gene: PHF21A was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: PHF21A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PHF21A were set to 36117209 Phenotypes for gene: PHF21A were set to Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, MIM# 618725 Review for gene: PHF21A was set to RED Added comment: First reported CAS case with a de novo frameshift PHF21A variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.27 | KDM5C |
Thomas Scerri gene: KDM5C was added gene: KDM5C was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: KDM5C was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: KDM5C were set to 36117209; 36434256 Phenotypes for gene: KDM5C were set to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type, MIM# 300534 Review for gene: KDM5C was set to RED Added comment: First reported CAS case with a de novo frameshift HNRNPK variant (Kaspi et al., 2022; PMID: 36117209). Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though. Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes. Sources: Expert list, Expert Review |
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| Speech apraxia v0.27 | HNRNPK |
Thomas Scerri gene: HNRNPK was added gene: HNRNPK was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPK were set to 36117209 Phenotypes for gene: HNRNPK were set to Au-Kline syndrome, MIM# 616580 Review for gene: HNRNPK was set to RED Added comment: First reported CAS case with a de novo nonsense HNRNPK variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.27 | ERF | Zornitza Stark Marked gene: ERF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.27 | ERF | Zornitza Stark Gene: erf has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.27 | ERF | Zornitza Stark Classified gene: ERF as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.27 | ERF | Zornitza Stark Gene: erf has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.26 | ZNF142 | Zornitza Stark Marked gene: ZNF142 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.26 | ZNF142 | Zornitza Stark Gene: znf142 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.26 | ZNF142 | Zornitza Stark Classified gene: ZNF142 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.26 | ZNF142 | Zornitza Stark Gene: znf142 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.25 | ZFHX4 | Zornitza Stark Marked gene: ZFHX4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.25 | ZFHX4 | Zornitza Stark Gene: zfhx4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.25 | ZFHX4 | Zornitza Stark Classified gene: ZFHX4 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.25 | ZFHX4 | Zornitza Stark Gene: zfhx4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.24 | WDR5 | Zornitza Stark Marked gene: WDR5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.24 | WDR5 | Zornitza Stark Gene: wdr5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.24 | WDR5 | Zornitza Stark Classified gene: WDR5 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.24 | WDR5 | Zornitza Stark Gene: wdr5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.23 | UPF2 | Zornitza Stark Marked gene: UPF2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.23 | UPF2 | Zornitza Stark Gene: upf2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.23 | UPF2 | Zornitza Stark Classified gene: UPF2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.23 | UPF2 | Zornitza Stark Gene: upf2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.22 | TNRC6B | Zornitza Stark Marked gene: TNRC6B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.22 | TNRC6B | Zornitza Stark Gene: tnrc6b has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.22 | TNRC6B | Zornitza Stark Classified gene: TNRC6B as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.22 | TNRC6B | Zornitza Stark Gene: tnrc6b has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.21 | SETD1A | Zornitza Stark Marked gene: SETD1A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.21 | SETD1A | Zornitza Stark Gene: setd1a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.21 | SETD1A | Zornitza Stark Classified gene: SETD1A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.21 | SETD1A | Zornitza Stark Gene: setd1a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.20 | SETBP1 | Zornitza Stark Marked gene: SETBP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.20 | SETBP1 | Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.20 | SETBP1 | Zornitza Stark Classified gene: SETBP1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.20 | SETBP1 | Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.19 | POGZ | Zornitza Stark Marked gene: POGZ as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.19 | POGZ | Zornitza Stark Gene: pogz has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.19 | POGZ | Zornitza Stark Classified gene: POGZ as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.19 | POGZ | Zornitza Stark Gene: pogz has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.18 | MEIS2 | Zornitza Stark Marked gene: MEIS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.18 | MEIS2 | Zornitza Stark Gene: meis2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.18 | MEIS2 | Zornitza Stark Classified gene: MEIS2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.18 | MEIS2 | Zornitza Stark Gene: meis2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.17 | GNB1 | Zornitza Stark Marked gene: GNB1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.17 | GNB1 | Zornitza Stark Gene: gnb1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.17 | GNB1 | Zornitza Stark Classified gene: GNB1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.17 | GNB1 | Zornitza Stark Gene: gnb1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.16 | GNAO1 | Zornitza Stark Marked gene: GNAO1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.16 | GNAO1 | Zornitza Stark Gene: gnao1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.16 | GNAO1 | Zornitza Stark Classified gene: GNAO1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.16 | GNAO1 | Zornitza Stark Gene: gnao1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.15 | EBF3 | Zornitza Stark Marked gene: EBF3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.15 | EBF3 | Zornitza Stark Gene: ebf3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.15 | EBF3 | Zornitza Stark Classified gene: EBF3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.15 | EBF3 | Zornitza Stark Gene: ebf3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.14 | DIP2C | Zornitza Stark Marked gene: DIP2C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.14 | DIP2C | Zornitza Stark Gene: dip2c has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.14 | DIP2C | Zornitza Stark Classified gene: DIP2C as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.14 | DIP2C | Zornitza Stark Gene: dip2c has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.13 | DDX3X | Zornitza Stark Marked gene: DDX3X as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.13 | DDX3X | Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.13 | DDX3X | Zornitza Stark Classified gene: DDX3X as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.13 | DDX3X | Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.12 | CDK13 | Zornitza Stark Marked gene: CDK13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.12 | CDK13 | Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.12 | CDK13 | Zornitza Stark Classified gene: CDK13 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.12 | CDK13 | Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.11 | BRPF1 | Zornitza Stark Marked gene: BRPF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.11 | BRPF1 | Zornitza Stark Gene: brpf1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.11 | BRPF1 | Zornitza Stark Classified gene: BRPF1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.11 | BRPF1 | Zornitza Stark Gene: brpf1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.10 | ARHGEF9 | Zornitza Stark Marked gene: ARHGEF9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.10 | ARHGEF9 | Zornitza Stark Gene: arhgef9 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.10 | ARHGEF9 | Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.9 | ARHGEF9 | Zornitza Stark Classified gene: ARHGEF9 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.9 | ARHGEF9 | Zornitza Stark Gene: arhgef9 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.8 | ERF |
Thomas Scerri gene: ERF was added gene: ERF was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: ERF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ERF were set to 36117209; 35761471; 35852485 Phenotypes for gene: ERF were set to Craniosynostosis 4, MIM# 600775 Review for gene: ERF was set to AMBER Added comment: First two reported CAS cases with a nonsense ERF variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband. Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder. Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments. Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | DIP2C |
Thomas Scerri gene: DIP2C was added gene: DIP2C was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DIP2C were set to 36117209; 38421105 Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO:0700092), DIP2C-related Review for gene: DIP2C was set to AMBER Added comment: First reported CAS proband with a de novo splice DIP2C variant (Kaspi et al., 2022; PMID: 36117209). Ha et al. (2024; PMID: 38421105) report 23 cases with various DIP2C variants, including the one published by Kaspi et al. (2022; PMID: 36117209). All 23 cases have various speech deficits and two (including the Kaspi et al. (2022) case) are reported having speech apraxia. Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | BRPF1 |
Thomas Scerri gene: BRPF1 was added gene: BRPF1 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: BRPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BRPF1 were set to 36117209; 27939640; 38346666 Phenotypes for gene: BRPF1 were set to Intellectual developmental disorder with dysmorphic facies and ptosis, MIM# 617333 Review for gene: BRPF1 was set to GREEN Added comment: First reported CAS proband with a de novo missense BRPF1 variant (Kaspi et al., 2022; PMID: 36117209). Yan et al. (2017; PMID: 27939640) reported 10 independent cases with de novo or inherited BRPF1 variants and with a range of speech and language deficits, including one proband with speech apraxia (proband 4, Table S1). Morison et al. (2024; PMID: 38346666) report 15 new cases with mostly de novo BRPF1 variants and a range of speech deficits, including 3 specifically with speech apraxia. Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | ARHGEF9 |
Thomas Scerri gene: ARHGEF9 was added gene: ARHGEF9 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: ARHGEF9 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: ARHGEF9 were set to 36117209 Phenotypes for gene: ARHGEF9 were set to Developmental and epileptic encephalopathy 8, MIM# 300607 Review for gene: ARHGEF9 was set to RED Added comment: Only reported CAS proband with a de novo nonsense ARHGEF9 variant (Kaspi et al., 2022; PMID: 36117209). Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | ZNF142 |
Thomas Scerri gene: ZNF142 was added gene: ZNF142 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: ZNF142 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF142 were set to 32345733; 31036918; 34531528; 35616059 Phenotypes for gene: ZNF142 were set to Neurodevelopmental disorder with impaired speech and hyperkinetic movements, MIM# 618425 Review for gene: ZNF142 was set to AMBER Added comment: A reported CAS proband with compound heterozygous missenses ZNF142 variants (Hildebrand et al., 2020; PMID: 32345733). Khan et al. (2019, PMID: 31036918) report 7 cases with compound heterozygous or else homozygous LoF or missense ZNF142 variants for which the cases have a range of speech deficits including speech apraxia in one case. Kameyama et al. (2020, PMID: 34531528) report two brothers with biallelic LoF ZNF142 variants for which the cases have speech deficits. Christensen et al. (2022; PMID: 35616059) report a further 26 individuals with biallelic ZNF142 variants for which the cases have a range of speech deficits. Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | UPF2 |
Thomas Scerri gene: UPF2 was added gene: UPF2 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: UPF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UPF2 were set to 32345733; 31585809 Phenotypes for gene: UPF2 were set to Neurodevelopmental disorder (MONDO:0700092), UPF2-related Review for gene: UPF2 was set to RED Added comment: A CAS proband with a de novo LoF UPF2 variant (Hildebrand et al., 2020; PMID: 32345733). Johnson et al. (2019; PMID: 31585809) report 3 independent cases with LoF UPF2 variants and a range of speech deficits, including speech apraxia in one of the cases (although the speech disorder had resolved to a mild phonological disorder at later testing). Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | POGZ |
Thomas Scerri gene: POGZ was added gene: POGZ was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POGZ were set to 32345733; 35052493 Phenotypes for gene: POGZ were set to White-Sutton syndrome, MIM# 616364 Review for gene: POGZ was set to RED Added comment: Only reported CAS proband with a de novo missense POGZ variant (Hildebrand et al., 2020; PMID: 32345733). Nagy et al. (2022; PMID: 35052493) reported 117 cases from a meta-analysis and found that "the most common symptoms were speech delay in 88%". This is not strong enough evidence to be supporting evidence for speech apraxia per se. Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | MEIS2 |
Thomas Scerri gene: MEIS2 was added gene: MEIS2 was added to Speech apraxia. Sources: Expert Review,Expert list Mode of inheritance for gene: MEIS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MEIS2 were set to 32345733; 30055086 Phenotypes for gene: MEIS2 were set to Cleft palate, cardiac defects, and impaired intellectual development, MIM# 600987 Review for gene: MEIS2 was set to AMBER Added comment: First reported CAS proband with a LoF MEI2 variant (Hildebrand et al., 2020; PMID: 32345733). Douglas et al. (2018; PMID: 30055086) report 3 new cases with de novo missense variants and 2 previously published deletion and nonsense variants. All cases have a range of differently worded speech problems, and one has verbal apraxia. Sources: Expert Review, Expert list |
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| Speech apraxia v0.8 | GNB1 |
Thomas Scerri gene: GNB1 was added gene: GNB1 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GNB1 were set to 32345733 Phenotypes for gene: GNB1 were set to Intellectual developmental disorder, autosomal dominant 42, MIM# 616973 Review for gene: GNB1 was set to RED Added comment: Only reported CAS proband with a de novo nonsense GNB1 variant (Hildebrand et al., 2020; PMID: 32345733). Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | GNAO1 |
Thomas Scerri gene: GNAO1 was added gene: GNAO1 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: GNAO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GNAO1 were set to 32345733; 35722775; 38881224 Phenotypes for gene: GNAO1 were set to Developmental and epileptic encephalopathy 17, MIM# 615473; Neurodevelopmental disorder with involuntary movements, MIM# 617493 Review for gene: GNAO1 was set to AMBER Added comment: First reported CAS proband with a de novo missense GNAO1 variant (Hildebrand et al., 2020; PMID: 32345733). These additional cases are less clear for speech apraxia: Wirth et al. (2020; PMID: 35722775) reported twenty-four independent cases with a range of de novo and inherited variants, including missense and nonsense, for which a speech disorder (dysarthria) was reported for 19 individuals. Lasa-Aranzasti et al. (2024; PMID: 38881224) report eighteen independent cases and find "all patients developed some type of nonverbal communication, but only four acquired verbal language." Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | EBF3 |
Thomas Scerri changed review comment from: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review; to: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Of these ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | EBF3 |
Thomas Scerri changed review comment from: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733). Chao et al., (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia. Sources: Expert list, Expert Review; to: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733). Chao et al. (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia. Deisseroth et al. (2022; PMID: 35340043) report a total of 83 individuals with missense or protein-truncating variants for EBF3 from a meta-analysis and find 10% have speech apraxia. Ten cases carried de novo EBF3 variants and were reported as having speech apraxia (supplementary tables). Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | DDX3X |
Thomas Scerri changed review comment from: First proband with a de novo LoF DDX3X variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733). Second proband with a de novo LoF DDX3X variant reported for CAS (Kaspi et al., 2022; PMID: 36117209) Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)". Sources: Expert list, Expert Review; to: First reported CAS proband with a de novo LoF DDX3X variant (Hildebrand et al., 2020; PMID: 32345733). Second reported CAS proband with a de novo LoF DDX3X variant (Kaspi et al., 2022; PMID: 36117209) Third in-house CAS proband with a de novo LoF DDX3X variant (not published). Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)". Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | TNRC6B | Thomas Scerri edited their review of gene: TNRC6B: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.8 | TNRC6B |
Thomas Scerri changed review comment from: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886). Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B. Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B. Sources: Expert list, Expert Review; to: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886). These additional supporting studies are for speech delay rather than speech apraxia per se: Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B. Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B. Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | SETD1A | Thomas Scerri edited their review of gene: SETD1A: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.8 | SETD1A | Thomas Scerri edited their review of gene: SETD1A: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.8 | SETD1A |
Thomas Scerri changed review comment from: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886). Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". Sources: Expert list, Expert Review; to: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886). Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1). Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | EBF3 |
Thomas Scerri gene: EBF3 was added gene: EBF3 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: EBF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EBF3 were set to 32345733; 28017372 Phenotypes for gene: EBF3 were set to Hypotonia, ataxia, and delayed development syndrome, MIM# 617330 Review for gene: EBF3 was set to GREEN Added comment: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733). Chao et al., (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia. Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | DDX3X |
Thomas Scerri gene: DDX3X was added gene: DDX3X was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: DDX3X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: DDX3X were set to 32345733; 36117209; 37904618 Phenotypes for gene: DDX3X were set to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, MIM# 300958 Review for gene: DDX3X was set to GREEN Added comment: First proband with a de novo LoF DDX3X variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733). Second proband with a de novo LoF DDX3X variant reported for CAS (Kaspi et al., 2022; PMID: 36117209) Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)". Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | CDK13 |
Thomas Scerri gene: CDK13 was added gene: CDK13 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: CDK13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDK13 were set to 32345733; 36599938 Phenotypes for gene: CDK13 were set to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, MIM# 617360 Review for gene: CDK13 was set to GREEN Added comment: First proband with a de novo missense CDK13 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733). Morison et al. (2023; PMID: 36599938) report 41 cases (with 33 novel variants) and find "most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22)." Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | ZFHX4 |
Thomas Scerri gene: ZFHX4 was added gene: ZFHX4 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZFHX4 were set to 29463886; 34461323 Phenotypes for gene: ZFHX4 were set to Neurodevelopmental disorder (MONDO:0700092), ZFHX4-related Review for gene: ZFHX4 was set to RED Added comment: First proband with splice acceptor ZFHX4 variant reported for CAS (Eising et al., 2019; PMID: 29463886). Fontana et al. (2021; PMID: 34461323) report a similar splice region variant in ZFHX4 for a proband with a neuropsychological phenotype, and summarise other probands with deletions or point mutations and associated phenotypes. Only one of these has a recorded speech phenotype. Overall this paper doesn't add strong evidence for a link between speech apraxia and ZFHX4. Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | WDR5 |
Thomas Scerri gene: WDR5 was added gene: WDR5 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: WDR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: WDR5 were set to 29463886; 36408368 Phenotypes for gene: WDR5 were set to Neurodevelopmental disorder (MONDO:0700092), WDR5-related Review for gene: WDR5 was set to GREEN Added comment: First proband with a de novo missense WDR5 variant reported for CAS (Eising et al., 2019; PMID: 29463886). Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering." Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | TNRC6B |
Thomas Scerri gene: TNRC6B was added gene: TNRC6B was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: TNRC6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TNRC6B were set to 29463886; 32152250; 38300321; 38404251 Phenotypes for gene: TNRC6B were set to Global developmental delay with speech and behavioral abnormalities, MIM# 619243 Review for gene: TNRC6B was set to GREEN Added comment: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886). Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)". Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B. Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B. Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | SETD1A |
Thomas Scerri gene: SETD1A was added gene: SETD1A was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: SETD1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SETD1A were set to 29463886; 32346159 Phenotypes for gene: SETD1A were set to Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056 Review for gene: SETD1A was set to GREEN Added comment: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886). Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | SETBP1 |
Thomas Scerri gene: SETBP1 was added gene: SETBP1 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: SETBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SETBP1 were set to 29463886; 33907317 Phenotypes for gene: SETBP1 were set to Intellectual developmental disorder, autosomal dominant 29, MIM# 616078 Review for gene: SETBP1 was set to GREEN Added comment: First proband with LoF SETBP1 variant reported for CAS (Eising et al., 2019; PMID: 29463886) Thirty one further probands with LoF SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%) being the most common diagnosis.". Sources: Expert list, Expert Review |
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| Speech apraxia v0.8 | MKL2 |
Zornitza Stark changed review comment from: Only two individuals reported.; to: Only two individuals reported with GoF variants. The variant reported in a third individual in PMID 29463886 is present in >500 individuals in gnomAD v4, and is marked as LCLoF. |
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| Speech apraxia v0.8 | MKL2 | Zornitza Stark edited their review of gene: MKL2: Changed publications: 29463886 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.8 | CHD3 | Zornitza Stark Marked gene: CHD3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.8 | CHD3 | Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.8 | CHD3 | Zornitza Stark Phenotypes for gene: CHD3 were changed from to Snijders Blok-Campeau syndrome MIM#618205 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.7 | CHD3 | Zornitza Stark Classified gene: CHD3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.7 | CHD3 | Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.6 | CHD3 | Zornitza Stark reviewed gene: CHD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30397230; Phenotypes: Snijders Blok-Campeau syndrome MIM#618205; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.6 | KAT6A | Zornitza Stark Marked gene: KAT6A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.6 | KAT6A | Zornitza Stark Gene: kat6a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.6 | KAT6A | Zornitza Stark Phenotypes for gene: KAT6A were changed from Childhood apraxia of speech; see comments. to Arboleda-Tham syndrome, MIM# 616268 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.5 | KAT6A | Zornitza Stark Classified gene: KAT6A as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.5 | KAT6A | Zornitza Stark Gene: kat6a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.4 | KAT6A | Zornitza Stark reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: None; Publications: 35892268; Phenotypes: Arboleda-Tham syndrome, MIM# 616268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.4 | MKL2 | Zornitza Stark Marked gene: MKL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.4 | MKL2 | Zornitza Stark Gene: mkl2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.4 | MKL2 | Zornitza Stark Phenotypes for gene: MKL2 were changed from Childhood apraxia of speech; see comments. to Neurodevelopmental disorder (MONDO:0700092), MKL2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.3 | MKL2 | Zornitza Stark Classified gene: MKL2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.3 | MKL2 | Zornitza Stark Gene: mkl2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.2 | MKL2 | Zornitza Stark reviewed gene: MKL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), MKL2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.2 | FOXP2 | Zornitza Stark Marked gene: FOXP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.2 | FOXP2 | Zornitza Stark Gene: foxp2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.2 | FOXP2 | Zornitza Stark Phenotypes for gene: FOXP2 were changed from Childhood apraxia of speech to Speech-language disorder-1, MIM# 602081 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.1 | FOXP2 | Zornitza Stark Classified gene: FOXP2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.1 | FOXP2 | Zornitza Stark Gene: foxp2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | FOXP2 | Zornitza Stark reviewed gene: FOXP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Speech-language disorder-1, MIM# 602081; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | MKL2 |
Thomas Scerri changed review comment from: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023). Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112). Sources: Expert list, Expert Review; to: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023). Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112). Sources: Expert list, Expert Review |
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| Speech apraxia v0.0 | KAT6A |
Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112). Sources: Expert list, Expert Review; to: Additional phenotypes: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112). Sources: Expert list, Expert Review |
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| Speech apraxia v0.0 | FOXP2 | Thomas Scerri changed review comment from: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112).; to: Additional phenotypes: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).; to: Additional phenotypes: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | FOXP2 | Thomas Scerri edited their review of gene: FOXP2: Changed publications: 11586359, 36328423, 38366112 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri edited their review of gene: CHD3: Changed publications: 30397230, 38366112, 35346573 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | MKL2 | Thomas Scerri edited their review of gene: MKL2: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | MKL2 |
Thomas Scerri changed review comment from: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023). Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues. AT Morgan et al., (2024). Sources: Expert list, Expert Review; to: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023). Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues (PMID: 38366112). Sources: Expert list, Expert Review |
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| Speech apraxia v0.0 | KAT6A |
Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. (PMID: 38366112). Sources: Expert list, Expert Review; to: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112). Sources: Expert list, Expert Review |
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| Speech apraxia v0.0 | FOXP2 | Thomas Scerri changed review comment from: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. (PMID: 38366112).; to: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance (PMID: 38366112). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. (PMID: 38366112).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | KAT6A |
Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al., (2024). Sources: Expert list, Expert Review; to: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. (PMID: 38366112). Sources: Expert list, Expert Review |
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| Speech apraxia v0.0 | FOXP2 | Thomas Scerri changed review comment from: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. AT Morgan et al., (2024).; to: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. (PMID: 38366112). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al., (2024).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. (PMID: 38366112). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al. (2024).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al., (2024). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | KAT6A |
Thomas Scerri changed review comment from: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al. (2024). Sources: Expert list, Expert Review; to: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al., (2024). Sources: Expert list, Expert Review |
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| Speech apraxia v0.0 | MKL2 |
Thomas Scerri gene: MKL2 was added gene: MKL2 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: MKL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MKL2 were set to 29463886; 37013900; 38366112 Phenotypes for gene: MKL2 were set to Childhood apraxia of speech; see comments. Penetrance for gene: MKL2 were set to Complete Added comment: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023). Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues. AT Morgan et al., (2024). Sources: Expert list, Expert Review |
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| Speech apraxia v0.0 | KAT6A |
Thomas Scerri gene: KAT6A was added gene: KAT6A was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KAT6A were set to 35892268; 38366112; 30245513 Phenotypes for gene: KAT6A were set to Childhood apraxia of speech; see comments. Penetrance for gene: KAT6A were set to Complete Review for gene: KAT6A was set to GREEN Added comment: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al. (2024). Sources: Expert list, Expert Review |
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| Speech apraxia v0.0 | CHD3 | Thomas Scerri edited their review of gene: CHD3: Added comment: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al. (2024).; Changed phenotypes: Childhood apraxia of speech, see comments. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | FOXP2 | Thomas Scerri edited their review of gene: FOXP2: Added comment: Cognition ranges from average to mild ID, feeding difficulties in infancy, fine & gross motor impairment, ASD, language impairment, anxiety, depression, sleep disturbance. AT Morgan et al., (2024).; Changed phenotypes: Childhood apraxia of speech, see comments. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri edited their review of gene: CHD3: Changed phenotypes: Childhood apraxia of speech | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 |
Thomas Scerri gene: CHD3 was added gene: CHD3 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CHD3 were set to PMID: 30397230; 38366112; 35346573 Penetrance for gene: CHD3 were set to Complete Review for gene: CHD3 was set to GREEN Added comment: Variant p.Leu915Phe yielded increased activity (PMID: 30397230). Evidence of reduced penetrance and variable expressivity (PMID: 35346573). Sources: Expert list, Expert Review |
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| Speech apraxia v0.0 | FOXP2 |
Thomas Scerri gene: FOXP2 was added gene: FOXP2 was added to Speech apraxia. Sources: Expert list,Expert Review Mode of inheritance for gene: FOXP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOXP2 were set to PMID: 11586359; 36328423; 38366112 Phenotypes for gene: FOXP2 were set to Childhood apraxia of speech Penetrance for gene: FOXP2 were set to Complete Review for gene: FOXP2 was set to GREEN Added comment: Sources: Expert list, Expert Review |
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| Speech apraxia v0.0 | Zornitza Stark Added Panel Speech apraxia | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||