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| Fetal anomalies v1.167 | EFCAB1 | Zornitza Stark Phenotypes for gene: EFCAB1 were changed from Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related to Ciliary dyskinesia, primary, 53, MIM# 620642 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.166 | EFCAB1 | Zornitza Stark edited their review of gene: EFCAB1: Added comment: HGNC approved name is CLXN; Changed phenotypes: Ciliary dyskinesia, primary, 53, MIM# 620642 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.160 | MFN2 |
Andrew Fennell gene: MFN2 was added gene: MFN2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MFN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MFN2 were set to PMID: 37804319 Phenotypes for gene: MFN2 were set to Mitochondrial disease, MONDO:0044970, MFN2-related Review for gene: MFN2 was set to AMBER Added comment: A single report of fetus with severe antenatal encephalopathy with lissencephaly, polymicrogyria, and cerebellar atrophy. The authors identified a homozygous in-frame deletion leading to exon 16 skipping and in-frame loss of 50 amino acids 13 (p.Gln574_Val624del). Functional evidence of mitochondrial dysfunction (clumping) and respiratory chain complex deficiencies. Sources: Literature |
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| Fetal anomalies v1.142 | DBR1 |
Chern Lim edited their review of gene: DBR1: Added comment: PMID: 37656279: - A homozygous missense as a founder recessive DBR1 variant in four consanguineous families. - Total of 7 affected children. WES done for one proband from each family. - Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life. - RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample. - Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant. - Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency.; Changed phenotypes: Ichthyosis (MONDO#0019269), DBR1-related |
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| Fetal anomalies v1.140 | DBR1 |
Chern Lim gene: DBR1 was added gene: DBR1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DBR1 were set to 37656279 Phenotypes for gene: DBR1 were set to Prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation, and death before the first year of life Review for gene: DBR1 was set to AMBER gene: DBR1 was marked as current diagnostic Added comment: PMID: 37656279: - A homozygous missense as a founder recessive DBR1 variant in four consanguineous families. - Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life. - RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample. - Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant. - Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency. Sources: Literature |
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| Fetal anomalies v1.132 | PHF5A |
Daniel Flanagan gene: PHF5A was added gene: PHF5A was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: PHF5A were set to PMID: 37422718 Review for gene: PHF5A was set to GREEN Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects and heart defects, inguinal hernia, and sacral dimple in three subjects. Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects. Sources: Expert list |
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| Fetal anomalies v1.114 | BRWD1 | Zornitza Stark Phenotypes for gene: BRWD1 were changed from Situs inversus; primary ciliary dyskinesia like to Situs inversus; Ciliary dyskinesia, primary, 51, MIM# 620438 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.93 | FILIP1 |
Paul De Fazio gene: FILIP1 was added gene: FILIP1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FILIP1 were set to 36943452 Phenotypes for gene: FILIP1 were set to Arthrogryposis multiplex congenita MONDO:0015168 Penetrance for gene: FILIP1 were set to unknown Review for gene: FILIP1 was set to GREEN gene: FILIP1 was marked as current diagnostic Added comment: 3 families, all consanguineous, reported with 3 different homozygous loss of function variants (2x NMD-predicted nonsense, 1x intragenic deletion of exons 3-6 of 6). In one family, the variant segregated in 3 affected siblings. Phenotypes consist of congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly (-1.5 to -4 SD), and facial dysmorphism. Sources: Literature |
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| Fetal anomalies v1.87 | EFCAB1 |
Zornitza Stark gene: EFCAB1 was added gene: EFCAB1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: EFCAB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EFCAB1 were set to 36727596 Phenotypes for gene: EFCAB1 were set to Primary ciliary dyskinesia, MONDO:0016575, EFCAB1-related Review for gene: EFCAB1 was set to GREEN Added comment: WES in 3 individuals with laterality defects and respiratory symptoms, identified homozygous pathogenic variants in CLXN (EFCAB1). They found Clxn expressed in mice left-right organizer. Transmission electron microscopy depicted outer dynein arm (ODA) defects in distal ciliary axonemes. Immunofluorescence microscopy revealed absence of CLXN from the ciliary axonemes, absence of the ODA components DNAH5, DNAI1 and DNAI2 from the distal axonemes, as well as mislocalization or absence of DNAH9. Additionally, CLXN is undetectable in ciliary axonemes of individuals with defects in the outer dynein arm docking (ODA-DC) machinery: ODAD1, ODAD2, ODAD3 and ODAD4. Moreover, SMED-EFCAB1-deficient planaria displayed ciliary dysmotility. Sources: Literature |
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| Fetal anomalies v0.4513 | PRKD1 |
Zornitza Stark edited their review of gene: PRKD1: Added comment: PMID: 27479907 (2016): three individuals reported, two with the c.1774G>A variant and one with the c.896T>G variant. All had congenital heart disease, two had some developmental delay, and two had variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth; the third individuals had a 'disorganized eyebrow.' PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, and telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. Functional analysis using in vitro kinase assays with recombinant proteins showed that the c.1808G>A, p.(Arg603His) variant represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The c.1774G>C, p.(Gly592Arg) variant in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation. c.1774G>C, p.(Gly592Arg) is recurrent, reported in 3/5 individuals.; Changed publications: 27479907, 32817298; Changed phenotypes: Congenital heart defects and ectodermal dysplasia, MIM#617364; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Fetal anomalies v0.4305 | VPS50 |
Chirag Patel gene: VPS50 was added gene: VPS50 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS50 were set to PMID: 34037727 Phenotypes for gene: VPS50 were set to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685 Review for gene: VPS50 was set to AMBER Added comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants. Common features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. Both individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)). VPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor. As discussed by Schneeberger et al (refs provided in text): - VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development. - Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality. Studies performed by Schneeberger et al included: - Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del). - Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels. - Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts. - Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function. As the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term "GARP and/or EARP deficiency disorders". There is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes. Sources: Expert list |
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| Fetal anomalies v0.4295 | YIF1B |
Chirag Patel gene: YIF1B was added gene: YIF1B was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YIF1B were set to PMID: 32006098; 26077767 Phenotypes for gene: YIF1B were set to Kaya-Barakat-Masson syndrome, MIM# 619125 Review for gene: YIF1B was set to GREEN Added comment: Kaya-Barakat-Masson syndrome (KABAMAS) is a severe autosomal recessive neurodevelopmental disorder characterized by profoundly impaired global development, peripheral spasticity, dystonia, impaired intellectual development with absent speech, poor eye contact, and feeding difficulties, resulting in poor overall growth, sometimes with microcephaly. Additional more variable features include early-onset seizures, ocular anomalies, foot deformities, and nonspecific brain imaging findings, such as thin corpus callosum and cerebral, cerebellar, or pontine atrophy. Some patients may die in infancy or early childhood. 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function. Sources: Expert list |
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| Fetal anomalies v0.4290 | PIDD1 |
Daniel Flanagan gene: PIDD1 was added gene: PIDD1 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIDD1 were set to 28397838; 29302074; 33414379; 34163010 Phenotypes for gene: PIDD1 were set to Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum Review for gene: PIDD1 was set to AMBER Added comment: Doesn't appear to have an antenatal onset. Clinical findings in supplementary table for PMID: 34163010 doesn't mention any prenatal findings. For family M278, two affected siblings were "born at term after uneventful pregnancies, neonatal periods and normal development." Mean age of cohort was 13.2 years. Biallelic PIDD1 pathogenic variants have been reported in 26 individuals (11 families) with DD (all), variable degrees of ID (mild to severe), behavioral (eg. aggression/self-mutilation in several, ADHD) and/or psychiatric abnormalities (ASD, psychosis in 5 belonging to 3 families), well-controlled epilepsy is some (9 subjects from 6 families) and MRI abnormalities notably abnormal gyration pattern (pachygyria with predominant anterior gradient) as well as corpus callosum anomalies (commonly thinning) in several. Dysmorphic features have been reported in almost all, although there has been no specific feature suggested. The first reports on the phenotype associated with biallelic PIDD1 mutations were made by Harripaul et al (2018 - PMID: 28397838) and Hu et al (2019 - PMID: 29302074) [both studies investigating large cohorts of individuals with ID from consanguineous families]. Sheikh et al (2021 - PMID: 33414379) provided details on the phenotype of 15 individuals from 5 families including those from the previous 2 reports and studied provided evidence on the role of PIDD1 and the effect of variants. Zaki et al (2021 - PMID: 34163010) reported 11 additional individuals from 6 consanguineous families, summarize the features of all subjects published in the literature and review the neuroradiological features of the disorder. PIDD1 encodes p53-induced death domain protein 1. The protein is part of the PIDDosome, a multiprotein complex also composed of the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 and induces apoptosis in response to DNA damage. There are 5 potential PIDD1 mRNA transcript variants with NM_145886.4 corresponding to the longest. Similar to the protein encoded by CRADD, PIDD1 contains a death domain (DD - aa 774-893). Constitutive post-translational processing gives PIDD1-N, PIDD1-C the latter further processed into PIDD1-CC (by auto-cleavage). Serine residues at pos. 446 and 588 are involved in this autoprocessing generating PIDD1-C (aa 446-910) and PIDD1-CC (aa 774-893). The latter is needed for caspase-2 activation. Most (if not all) individuals belonged to consanguineous families of different origins and harbored pLoF or missense variants. Variants reported so far include : c.2587C>T; p.Gln863* / c.1909C>T ; p.Arg637* / c.2443C>T / p.Arg815Trp / c.2275-1G>A which upon trap assay was shown to lead to skipping of ex15 with direct splicing form exon14 to the terminal exon 16 (resulting to p.Arg759Glyfs*1 with exlcusion of the entire DD) / c.2584C>T; p.Arg862Trp / c.1340G>A; p.Trp447* / c.2116_2120del; p.Val706His*, c.1564_1565del; p.Gly602fs*26 Evidence so far provided includes: - Biallelic CRADD variants cause a NDD disorder and a highly similar gyration pattern. - Confirmation of splicing effect (eg. for c.2275-1G>A premature stop in position 760) or poor expression (NM_145886.3:c.2587C>T; p.Gln863*). Arg815Trp did not affect autoprocessing or protein stability. - Abnormal localization pattern, loss of interaction with CRADD and failure to activate caspase-2 (MDM2 cleavage assay) [p.Gln863* and Arg815Trp] - Available expression data from GTEx (PIDD1 having broad expression in multiple tissues, but higher in brain cerebellum) as well as BrainSpan and PsychEncode studies suggesting high coexpression of PIDD1, CRADD and CASP2 in many regions in the developing human brain. - Variants in other genes encoding proteins interacting with PIDD1 (MADD, FADD, DNAJ, etc) are associated with NDD. Pidd-1 ko mice (ex3-15 removal) lack however CNS-related phenotypes. These show decreased anxiety but no motor anomalies. This has also been the case with Cradd-/- mice displaying no significant CNS phenotypes without lamination defects. Sources: Expert list |
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| Fetal anomalies v0.4255 | PPP2R3C |
Chirag Patel gene: PPP2R3C was added gene: PPP2R3C was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818 Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419 Review for gene: PPP2R3C was set to GREEN Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility. Sources: Literature |
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| Fetal anomalies v0.4253 | UNC13A |
Belinda Chong gene: UNC13A was added gene: UNC13A was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: UNC13A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: UNC13A were set to 27648472; 28192369 Phenotypes for gene: UNC13A were set to Congenital myasthenia; dyskinesia; autism; developmental delay Review for gene: UNC13A was set to RED Added comment: One individual described with biallelic variants in this gene and a myasthenic syndrome; another individual reported with de novo variant in this gene and a different neurological phenotype (abnormal movements, developmental delay and autism). Sources: Literature |
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| Fetal anomalies v0.4134 | SPAG1 | Seb Lunke Phenotypes for gene: SPAG1 were changed from PRIMARY CILIARY DYSKINESIA ASSOCIATED WITH DEFECTIVE OUTER AND INNER DYNEIN ARMS. to Ciliary dyskinesia, primary, 28 (MIM#615505) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4122 | SPRED1 |
Zornitza Stark changed review comment from: Multiple affected individuals reported, deletions account for ~10% of causative variants. Legius syndrome is characterised by multiple cafe-au-lait spots, sometimes associated with skin fold freckling, variable dysmorphic features such as hypertelorism or macrocephaly, lipomas, and mild learning disabilities or attention problems. It is not associated with neurofibromas, optic gliomas, Lisch nodules, or tumor predisposition. The SPRED1 gene encodes a negative regulator of the RAS-MAPK pathway, similar to neurofibromin.; to: Multiple affected individuals reported, deletions account for ~10% of causative variants. Legius syndrome is characterised by multiple cafe-au-lait spots, sometimes associated with skin fold freckling, variable dysmorphic features such as hypertelorism or macrocephaly, lipomas, and mild learning disabilities or attention problems. It is not associated with neurofibromas, optic gliomas, Lisch nodules, or tumor predisposition. The SPRED1 gene encodes a negative regulator of the RAS-MAPK pathway, similar to neurofibromin. Clinical presentation is typically post-natal. |
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| Fetal anomalies v0.4083 | TCTN3 | Zornitza Stark Phenotypes for gene: TCTN3 were changed from MOHR-MAJEWSKI SYNDROME to Joubert syndrome 18, OMIM #614815; Orofaciodigital syndrome IV, OMIM #258860 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4032 | TRIP4 | Zornitza Stark Phenotypes for gene: TRIP4 were changed from Prenatal-onset spinal muscular atrophy with congenital bone fractures, MONDO:0000209; Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, MONDO:0014896; ?Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066; Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866; Spinal muscular atrophy with congenital bone fractures 1, MONDO:0014806 to Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866; Spinal muscular atrophy with congenital bone fractures 1, MONDO:0014806 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.4023 | TUBB | Zornitza Stark Phenotypes for gene: TUBB were changed from CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 6; Circumferential Skin Creases Kunze Type to Cortical dysplasia, complex, with other brain malformations 6, MIM#615771 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3930 | SKIV2L | Zornitza Stark Marked gene: SKIV2L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3930 | SKIV2L | Zornitza Stark Gene: skiv2l has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3930 | SKIV2L | Zornitza Stark Phenotypes for gene: SKIV2L were changed from TRICHOHEPATOENTERIC SYNDROME 2 to Trichohepatoenteric syndrome 2, MIM#614602 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3929 | SKIV2L | Zornitza Stark Classified gene: SKIV2L as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3929 | SKIV2L | Zornitza Stark Gene: skiv2l has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3928 | SKIV2L | Zornitza Stark reviewed gene: SKIV2L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichohepatoenteric syndrome 2, MIM#614602; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3908 | MAPK1 |
Krithika Murali gene: MAPK1 was added gene: MAPK1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAPK1 were set to 32721402 Phenotypes for gene: MAPK1 were set to Noonan syndrome 13 - MIM#619087 Review for gene: MAPK1 was set to GREEN Added comment: Associated with Noonan syndrome including congenital heart defects. No new publications since last PanelApp review Aug 2020 -- Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants. The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once. MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway. MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic). The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome). Sources: Literature |
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| Fetal anomalies v0.3908 | PLOD3 |
Krithika Murali gene: PLOD3 was added gene: PLOD3 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PLOD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLOD3 were set to 30237576; 18834968 Phenotypes for gene: PLOD3 were set to Lysyl hydroxylase 3 deficiency - MIM#612394 Review for gene: PLOD3 was set to GREEN Added comment: 4 unrelated families reported with biallelic PLOD3 variants and Stickler-syndrome like phenotype including antenatal phenotype of IUGR in one family. -- PMID 30237576 Maddirevula et al 2019 - report homozygous nonsense variant in a proband with dysmorphic facies, microcephaly, ptosis and contractures. No antenatal information provided. PMID 31129566 Ewans et al 2019 - report 3 affected siblings with a Stickler-syndrome like disorder. - Patient 1 had congenital nystagmus and presented with hearing loss and myopia. On examination aged 2, noted to have dysmorphic features - prominent eyes, hypertelorism, malar hypoplasia, an upturned nose, low-set ears and microretrognathia. - Patient 2 noted to have camptodactyly and clinodactyly postnatally. On examination age 5 noted to have DIP joint contractures and mild skin syndactyly. - Patient 3 - breech delivery. bilateral hand foot camptodactyly, facial dysmorphism. - No antenatal features reported. PMID 30463024 Vahidnehzad et al 2019 - report a male proband from a consanguineous Iranian Baloch family referred for assessment age 4.5. Noted to have developmental delay, musculoskeletal manifestations including scoliosis, flexion contractions, cutaneous syndactyly, right diaphragmatic eventration, ocular anomalies, growth failure and skin blisters. No concerns antenatally. Postnatally noted to have cataract and facial dysmorphism (midface hypoplasia). Homozygous PLOD3 missense variant identified, parents unaffected carriers. PLOD3 mRNA levels in the patient’s fibroblasts measured by whole-transcriptome sequencing and confirmed by RT-PCR, were the same as in control cells, however, the expression of type VII collagen was reduced significantly. No antenatal features reported. PMID: 18834968 Salo et al 2008 - a female proband with significant IUGR, characteristic craniofacial profile, diaphragm eventration, skeletal anomalies (bilateral talipes equinovarus, flexion contractures, scoliosis from age 7), skin anomalies incl blistering and ocular anomalies. One 28 week male stillborn sibling noted to have significant IUGR and skeletal anomalies on post-mortem. Supportive functional evidence. Compound het PLOD3 variants. Sources: Literature |
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| Fetal anomalies v0.3905 | RSPH3 | Zornitza Stark Phenotypes for gene: RSPH3 were changed from PRIMARY CILIARY DYSKINESIA WITH CENTRAL-COMPLEX DEFECTS to Ciliary dyskinesia, primary, 32 (MIM#616481) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3903 | RSPH1 | Zornitza Stark Phenotypes for gene: RSPH1 were changed from PRIMARY CILIARY DYSKINESIA WITH CENTRAL-COMPLEX AND RADIAL-SPOKE DEFECTS to Ciliary dyskinesia, primary, 24 (MIM#615481) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3889 | PTDSS1 | Zornitza Stark Phenotypes for gene: PTDSS1 were changed from LENZ-MAJEWSKI HYPEROSTOTIC DWARFISM to Lenz-Majewski hyperostotic dwarfism MIM#151050 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3886 | PTDSS1 | Zornitza Stark reviewed gene: PTDSS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24241535, 29341480, 31403251; Phenotypes: Lenz-Majewski hyperostotic dwarfism MIM#151050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3869 | PRRT2 | Zornitza Stark Phenotypes for gene: PRRT2 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; BENIGN FAMILIAL INFANTILE EPILEPSY AND INFANTILE CONVULSIONS WITH CHOREOATHETOSIS SYNDROME to Convulsions, familial infantile, with paroxysmal choreoathetosis, MIM# 602066; Episodic kinesigenic dyskinesia 1, MIM# 128200; Seizures, benign familial infantile, 2, MIM# 605751; intellectual disability, autosomal recessive | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3706 | HYDIN | Zornitza Stark Phenotypes for gene: HYDIN were changed from CILIARY DYSKINESIA, PRIMARY, 5 to Ciliary dyskinesia, primary, 5 (MIM#08647) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3654 | GAS8 | Zornitza Stark Phenotypes for gene: GAS8 were changed from PRIMARY CILIARY DYSKINESIA to Ciliary dyskinesia, primary, 33, MIM# 616726 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3617 | DLAT | Zornitza Stark changed review comment from: Only two families with ID reported; third individual had paroxysmal dyskinesia.; to: Clinical presentation is typically post-natal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3610 | ST3GAL5 |
Zornitza Stark changed review comment from: Salt and pepper developmental regression syndrome, also known as Amish infantile epilepsy syndrome, is an autosomal recessive neurocutaneous disorder characterised by infantile onset of refractory and recurrent seizures associated with profoundly delayed psychomotor development and/or developmental regression as well as abnormal movements and visual loss. Affected individuals develop hypo- or hyperpigmented skin macules on the trunk, face, and extremities in early childhood. Although initially reported in the Amish (founder variant p.Arg288Ter), families from other ethnicities have also been reported.; to: Salt and pepper developmental regression syndrome, also known as Amish infantile epilepsy syndrome, is an autosomal recessive neurocutaneous disorder characterised by infantile onset of refractory and recurrent seizures associated with profoundly delayed psychomotor development and/or developmental regression as well as abnormal movements and visual loss. Affected individuals develop hypo- or hyperpigmented skin macules on the trunk, face, and extremities in early childhood. Although initially reported in the Amish (founder variant p.Arg288Ter), families from other ethnicities have also been reported. Clinical presentation is typically post-natal. |
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| Fetal anomalies v0.3608 | RSPH9 | Zornitza Stark Phenotypes for gene: RSPH9 were changed from Ciliary dyskinesia, primary 612650 to Ciliary dyskinesia, primary, MIM# 612650 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3567 | RIN2 | Zornitza Stark Phenotypes for gene: RIN2 were changed from MACROCEPHALY, ALOPECIA, CUTIS LAXA, AND SCOLIOSIS TALL FOREHEAD, SPARSE HAIR, SKIN HYPEREXTENSIBILITY, AND SCOLIOSIS to Macrocephaly, alopecia, cutis laxa, and scoliosis, MIM#613075 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3413 | COQ7 |
Krithika Murali gene: COQ7 was added gene: COQ7 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: COQ7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COQ7 were set to 33215859; 28125198; 31240163; 28409910; 26084283 Phenotypes for gene: COQ7 were set to Coenzyme Q10 deficiency, primary, 8 - MIM#616733 Review for gene: COQ7 was set to GREEN Added comment: Biallelic variants associated with primary coenzyme Q10 (CoQ10) deficiency, a heterogeneous multi-system disorder including early-postnatal features such as neonatal encephalopathy, contractures. Antenatal features reported include IUGR, oligohydramnios, feetal lung hypoplasia, dysplastic kidneys. Specifically for COQ7-related CoQ10 deficiency: PMID 33215859 Hashemi et al 2020 - report two affected individuals from a consanguineous Iranian family with homozygous COQ7 variants progressive spastic paraparesis diagnosed at age 1.5-2 with normal antenatal history. PMID 31240163 Kwong et al 2019 - report a patient with compound hetereozygous COQ7 variants, encephalo‐myo‐nephro‐cardiopathy, persistent lactic acidosis, and basal ganglia lesions resulting in early infantile death. Skin fibroblast studies showed decreased combined complex II + III activity and reduction in CoQ10 level. The proband was a DCDA twin, noted to have IUGR, oligohydramnios, cardiomegaly and tricuspid regurgitation antenatally. PMID 28409910 Wang et al 2017 - no antenatal features reported in their proband PMID 26084283 Freyer et al 2015 - report x1 patient with homozygous COQ7 variant. The pregnancy was complicated by oligohydramniosis, fetal lung hypoplasia and growth retardation. Sources: Literature |
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| Fetal anomalies v0.3400 | RNU12 |
Krithika Murali gene: RNU12 was added gene: RNU12 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: RNU12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNU12 were set to 34085356 Phenotypes for gene: RNU12 were set to CDAGS syndrome MIM#603116; Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations Review for gene: RNU12 was set to GREEN Added comment: No new publications since last PanelApp review July 2021 --- 5 CDAGS syndrome families with biallelic variants all including NC_000022.10:g.43011402C>T and another variant on the second allele. Whole transcriptome sequencing analysis of patient lymphoblastoid cells identified differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events. Sources: Literature |
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| Fetal anomalies v0.3372 | SMARCAL1 |
Daniel Flanagan changed review comment from: Well-established gene-disease association; over 40 patients with biallelic mutations in SMARCAL1; Zebrafish and mouse models that recapitulates phenotype have been reported. This disorder combines abnormality of the immune and skeletal systems. Primary features include growth retardation (IUGR in 50%), renal failure, cerebral infarcts, skin pigmentation and CID (lymphocytopaenia, recurrent infections and/or T-cell immunodeficiency) beginning in childhood. GeneReviews: Short stature (99% of individuals) that typically manifests as a short neck and trunk with lumbar lordosis and a protruding abdomen.; to: Well-established gene-disease association; over 40 patients with biallelic mutations in SMARCAL1; Zebrafish and mouse models that recapitulates phenotype have been reported. This disorder combines abnormality of the immune and skeletal systems. Primary features include growth retardation (IUGR in 50%), renal failure, cerebral infarcts, skin pigmentation and CID (lymphocytopaenia, recurrent infections and/or T-cell immunodeficiency) beginning in childhood. GeneReviews: Short stature (99% of individuals) that typically manifests as a short neck and trunk with lumbar lordosis and a protruding abdomen. Most affected children have prenatal and postnatal disproportionate growth failure. A few have normal intrauterine growth followed by postnatal growth failure. |
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| Fetal anomalies v0.3177 | SCN8A | Zornitza Stark Phenotypes for gene: SCN8A were changed from EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 13; COGNITIVE IMPAIRMENT WITH OR WITHOUT CEREBELLAR ATAXIA to Developmental and epileptic encephalopathy 13, MIM#614558, dominant and recessive; Myoclonus, familial, 2, MIM# 618364; paroxysmal kinesigenic dyskinesias; Cognitive impairment with or without cerebellar ataxia, MIM# 614306 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3151 | SCN8A | Ain Roesley reviewed gene: SCN8A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 13, MIM#614558, dominant and recessive, Myoclonus, familial, 2, MIM# 618364, paroxysmal kinesigenic dyskinesias, Cognitive impairment with or without cerebellar ataxia, MIM# 614306; Mode of inheritance: None; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2993 | NPM1 |
Krithika Murali gene: NPM1 was added gene: NPM1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: NPM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NPM1 were set to 31570891 Phenotypes for gene: NPM1 were set to Dyskeratosis congenita Review for gene: NPM1 was set to AMBER Added comment: Heterozygous variants identified in 2 patients with dyskeratosis congenita (DKC). x1 patient with NPM1 missense mutation presented with severe growth defects at birth, thumb abnormalities and thrombocytopenia. x1 patient with in-frame NPM1 deletion presented with skin pigmentation abnormalities, nail dystrophy, microcephaly, developmental delay, short stature, skeletal abnormalities in the radius and bone marrow failure by age 6. Some of these features may be amenable to antenatal detection. Sources: Literature |
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| Fetal anomalies v0.2984 | PDE10A | Zornitza Stark Phenotypes for gene: PDE10A were changed from Childhood-Onset Chorea with Bilateral Striatal Lesions to Dyskinesia, limb and orofacial, infantile-onset, MIM#616921; Striatal degeneration, autosomal dominant, MIM#616922 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2980 | PDE10A | Zornitza Stark edited their review of gene: PDE10A: Added comment: Both disorders typically present post-natally.; Changed rating: RED; Changed phenotypes: Dyskinesia, limb and orofacial, infantile-onset, MIM#616921, Striatal degeneration, autosomal dominant, MIM#616922; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2892 | UROS |
Krithika Murali gene: UROS was added gene: UROS was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UROS were set to 34187847; 34828434; 15065102 Phenotypes for gene: UROS were set to Porphyria, congenital erythropoietic - MIM#263700; hydrops fetalis; multiple congenital anomalies Review for gene: UROS was set to GREEN Added comment: Biallelic variants associated with congenital erytropoietic porphyria (CEP). PMID 34187847 Khalouaoui A et al 2021 report one infant with CEP secondary to homozygous UROS variants. Prenatal ultrasound at 25 weeks of gestation revealed an increased nuchal translucency and myocardial hypertrophy. PMID: 34828434 Arnaud et al 2021 - report one fetus miscarried in the 2nd trimester with 22 weeks ultrasound showing hyperechogenic small intestine with short femurs. Subsequent pregnancy MTOP after antenatal USS showed hygroma coli, ascites, short femurs, double outlet right ventricle. Genomic sequencing on stored fetal DNA samples confirmed homozygous UROS p.Cys73Arg variants in both fetuses. PMID 15065102 Lazebnik et al 2004 reported the prenatal findings of two siblings with CEP secondary to homozygous pathogenic C73R variants. 1st child - USS at 17.5 weeks gestation showed increased nuchal thickness (9.7mm) with mild ascites, pericardial effusion, and skin oedema which persisted on subsequent scans. 2nd child - 16 week USS showed increased nuchal thickness (8.7mm) with scalp oedema, ascites, pericardial effusion, skin oedema and hepatomegaly. Other cases with antenatal features, particularly non-immune hydrops, secondary to suspected CEP reported but not confirmed molecularly. Sources: Literature |
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| Fetal anomalies v0.2795 | MAPRE2 | Zornitza Stark Phenotypes for gene: MAPRE2 were changed from Symmetric circumferential skin creases, congenital, 2, 616734 to Symmetric circumferential skin creases, congenital, 2, MIM#616734 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2774 | LRRC6 | Zornitza Stark Phenotypes for gene: LRRC6 were changed from PRIMARY CILIARY DISKINESIA to Ciliary dyskinesia, primary, 19, MIM# 614935 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2764 | LMNA | Zornitza Stark Phenotypes for gene: LMNA were changed from LETHAL TIGHT SKIN CONTRACTURE SYNDROME; CARDIOMYOPATHY DILATED WITH HYPERGONADOTROPIC HYPOGONADISM; FAMILIAL PARTIAL LIPODYSTROPHY TYPE 2; HUTCHINSON-GILFORD PROGERIA SYNDROME; EMERY-DREIFUSS MUSCULAR DYSTROPHY TYPE 2; MUSCULAR DYSTROPHY CONGENITAL LMNA-RELATED; CHARCOT-MARIE-TOOTH DISEASE TYPE 2B1; MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY; HEART-HAND SYNDROME SLOVENIAN TYPE; CARDIOMYOPATHY DILATED TYPE 1A; LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 1B to Restrictive dermopathy, lethal, MIM# 275210; Mandibuloacral dysplasia, MIM# 248370 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2722 | ASTN1 |
Krithika Murali gene: ASTN1 was added gene: ASTN1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ASTN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASTN1 were set to 29706646; 11861479 Phenotypes for gene: ASTN1 were set to Polymicrogyria; hypoplastic corpus callosum Review for gene: ASTN1 was set to AMBER Added comment: No OMIM gene disease association. No updated evidence since previous PanelApp review April 2020. PMID 29706646 - Wiszniewski et al 2018 - genomic analysis of individuals with disorders of cortical development. Identified one individual with compound het ASTN1 variants with diffuse polymicrogyria, spastic tetraplegia, epilepsy and developmental delay. Second consanguineous family with two sisters with homozygous missense variant in ASTN1 had hypoplastic corpus callosum. Animal model demonstrates abnormal neuronal migration in Astn1-/- deficient mice (PMID 11861479). Sources: Literature |
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| Fetal anomalies v0.2719 | NDUFB11 | Zornitza Stark Phenotypes for gene: NDUFB11 were changed from Mitochondrial complex I deficiency, nuclear type 30 MIM#301021 to Mitochondrial complex I deficiency, nuclear type 30 MIM#301021; Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2718 | NDUFB11 | Zornitza Stark Phenotypes for gene: NDUFB11 were changed from MICROPHTHALMIA WITH LINEAR SKIN DEFECTS SYNDROME to Mitochondrial complex I deficiency, nuclear type 30 MIM#301021 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2574 | EXPH5 | Zornitza Stark Phenotypes for gene: EXPH5 were changed from INHERITED SKIN FRAGILITY to Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive, OMIM #615028 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2479 | ZMYND10 | Zornitza Stark Phenotypes for gene: ZMYND10 were changed from PRIMARY CILIARY DYSKINESIA-22 to Ciliary dyskinesia, primary, 22, MIM#615444 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2422 | TTC25 | Zornitza Stark Phenotypes for gene: TTC25 were changed from Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization to Ciliary dyskinesia, primary, 35 (MIM#617092) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2328 | DRC1 | Zornitza Stark Phenotypes for gene: DRC1 were changed from PRIMARY CILARY DYSKINEASIA to Ciliary dyskinesia, primary, 21, MIM# 615294 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2300 | DNAL1 | Zornitza Stark Phenotypes for gene: DNAL1 were changed from Ciliary dyskinesia, primary, 16, 614017 to Ciliary dyskinesia, primary, 16, MIM# 614017 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2296 | DNAI2 | Zornitza Stark Phenotypes for gene: DNAI2 were changed from Ciliary dyskinesia, primary, 9, with or without situs inversus,612444 to Ciliary dyskinesia, primary, 9, with or without situs inversus, MIM#612444 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2240 | HCCS | Zornitza Stark Phenotypes for gene: HCCS were changed from MICROPHTHALMIA SYNDROMIC TYPE 7 to Linear skin defects with multiple congenital anomalies 1, MIM# 309801 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1898 | TRPV4 | Zornitza Stark Phenotypes for gene: TRPV4 were changed from METATROPIC DYSPLASIA; SPONDYLOMETAPHYSEAL DYSPLASIA, KOZLOWSKI TYPE to Brachyolmia type 3, MIM# 113500; Metatropic dysplasia, MIM# 156530; SED, Maroteaux type, MIM# 184095; Spondylometaphyseal dysplasia, Kozlowski type, MIM# 184252 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1869 | TRPV4 | Alison Yeung reviewed gene: TRPV4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brachyolmia type 3, MIM# 113500, Metatropic dysplasia, MIM# 156530, SED, Maroteaux type, MIM# 184095, Spondylometaphyseal dysplasia, Kozlowski type, MIM# 184252; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1736 | SKI | Zornitza Stark reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Shprintzen-Goldberg syndrome, MIM#182212; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1725 | SKI | Seb Lunke Marked gene: SKI as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1725 | SKI | Seb Lunke Gene: ski has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1725 | SKI | Seb Lunke Publications for gene: SKI were set to 15884042; 23023332 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1724 | SKI | Seb Lunke Added comment: Comment on mode of pathogenicity: LoF not fully established on only missense described so far. Some functional work suggest potential GoF for TGF beta signalling, but not conclusive. Not enough evidence so far to go against LoF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1724 | SKI | Seb Lunke Mode of pathogenicity for gene: SKI was changed from to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1723 | SKI | Seb Lunke Phenotypes for gene: SKI were changed from SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME to Shprintzen-Goldberg syndrome, MIM#182212 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1722 | SKI | Seb Lunke Publications for gene: SKI were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1721 | SKI | Seb Lunke Mode of inheritance for gene: SKI was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1720 | SKI | Seb Lunke reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: None; Publications: 15884042, 23023332; Phenotypes: Shprintzen-Goldberg syndrome, MIM#182212; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1686 | CCNO | Zornitza Stark Phenotypes for gene: CCNO were changed from CILIARY DYSKINESIA, PRIMARY, 29 to Ciliary dyskinesia, primary, 29 615872 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1684 | CCDC65 | Zornitza Stark Phenotypes for gene: CCDC65 were changed from PRIMARY CILIARY DYSKINESIA to Ciliary dyskinesia, primary, 27, MIM# 615504 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1682 | CCDC65 |
Zornitza Stark changed review comment from: Same homozygous PTC (p.I293Pfs*2) reported in 3 Ashkenzi Jewish families. PMID: 24094744 performs functional assay on null zebrafish model - replicates human phenotype supporting LOF. Three different LoF reported in context of primary ciliary dyskinesia by diagnostic laboratories in ClinVar.; to: Same homozygous PTC (p.I293Pfs*2) reported in 3 Ashkenzi Jewish families. PMID: 24094744 performs functional assay on null zebrafish model - replicates human phenotype supporting LOF. Three different LoF reported in context of primary ciliary dyskinesia by diagnostic laboratories in ClinVar. Situs inversus not reported. |
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| Fetal anomalies v0.1587 | FGF3 | Zornitza Stark changed review comment from: Delay in gross motor skills thought to be related to balance issues, not truly ID.; to: Most features would not be detectable antenatally, but micrognathia may be evident. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1419 | CSTA | Zornitza Stark Phenotypes for gene: CSTA were changed from EXFOLIATIVE ICHTHYOSIS, AUTOSOMAL RECESSIVE, ICHTHYOSIS BULLOSA OF SIEMENS-LIKE to Peeling skin syndrome 4, MIM# 607936 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1417 | CSTA | Zornitza Stark reviewed gene: CSTA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Peeling skin syndrome 4, MIM# 607936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1361 | TTC12 |
Krithika Murali gene: TTC12 was added gene: TTC12 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TTC12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTC12 were set to 31978331 Phenotypes for gene: TTC12 were set to Ciliary dyskinesia, primary, 45 - MIM#618801 Review for gene: TTC12 was set to RED Added comment: Four unrelated families reported, LoF variants, respiratory phenotype. Sources: Literature |
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| Fetal anomalies v0.1361 | TP73 |
Krithika Murali gene: TP73 was added gene: TP73 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TP73 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TP73 were set to 31130284; 34077761 Phenotypes for gene: TP73 were set to Ciliary dyskinesia, primary, 47, and lissencephaly - MIM# 619466 Review for gene: TP73 was set to GREEN Added comment: 7 unrelated families reported. In vitro ciliogenesis experiments demonstrated that epithelial cells from TP73 variant carriers had reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controls. Clinical features included recurrent respiratory infections and respiratory dysfunction caused by defective mucociliary clearance in early childhood. Affected individuals also had neurologic features, such as impaired intellectual development and central hypotonia, associated with structural brain abnormalities, most notably lissencephaly and thin or absent corpus callosum. Sources: Literature |
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| Fetal anomalies v0.1361 | SPEF2 |
Krithika Murali gene: SPEF2 was added gene: SPEF2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SPEF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPEF2 were set to 31151990; 31278745; 31048344; 31942643 Phenotypes for gene: SPEF2 were set to Spermatogenic failure 43, MIM#618751; Primary ciliary dyskinesia-like phenotype Review for gene: SPEF2 was set to RED Added comment: Biallelic variants associated with sperm morphological abnormalities. In some individuals recurrent sinopulmonary infections and bronchiectasis noted consistent with PCD-like phenotype. Mouse model showed infertility phenotype, hydrocephalus, sinusitis. No fetal phenotype reported. Sources: Literature |
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| Fetal anomalies v0.1183 | CD96 |
Zornitza Stark changed review comment from: Intellectual disability is part of the phenotype. However, note one reported case ascribes causality based on translocation breakpoint, leaving only one other molecularly confirmed case with a missense variant. It is concerning no further cases have been reported, including in ClinVar, and no functional evidence is available.; to: The C syndrome, also known as Opitz trigonocephaly syndrome, is a malformation syndrome characterized by trigonocephaly, severe mental retardation, hypotonia, variable cardiac defects, redundant skin, and dysmorphic facial features, including upslanted palpebral fissures, epicanthal folds, depressed nasal bridge, and low-set, posteriorly rotated ears. However, note one reported case ascribes causality based on translocation breakpoint, leaving only one other molecularly confirmed case with a missense variant. It is concerning no further cases have been reported, including in ClinVar, and no functional evidence is available. |
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| Fetal anomalies v0.1104 | B9D1 | Zornitza Stark changed review comment from: PMID: 24886560 - 2 unrelated patients with mild Joubert syndrome patients found (1 hom missense, 1 chet inframe deletion/missense). Authors suggest biallelic null variants are lethal. PMID: 21493627 - 1 fetus with Meckell syndrome and chet for a splice/gene deletion. The splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP.; to: PMID: 21493627 - 1 fetus with Meckell syndrome and chet for a splice/gene deletion. The splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1104 | B9D1 | Zornitza Stark changed review comment from: PMID: 24886560 - 2 unrelated patients with mild Joubert syndrome patients found (1 hom missense, 1 chet inframe deletion/missense). Authors suggest biallelic null variants are lethal. PMID: 21493627 - 1 fetus with Meckell syndrome and chet for a splice/gene deletion. The splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. Authors perform functional studies on patient cells but given the large deletion/CEP290 variant i dont see the results are usable PMID: 25920555 - another report of digenic inheritance - not usable, patient was only heterozygous for a single B9D1 variant Summary: 2 unrelated patients, AMBER; to: PMID: 24886560 - 2 unrelated patients with mild Joubert syndrome patients found (1 hom missense, 1 chet inframe deletion/missense). Authors suggest biallelic null variants are lethal. PMID: 21493627 - 1 fetus with Meckell syndrome and chet for a splice/gene deletion. The splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1079 | DPM1 |
Zornitza Stark changed review comment from: PMID: 16641202 - 2 siblings of consanguineous parents. One patient showed retarded motor skills at 1, 2 and 4 years old, with distal myopathy present at 3 years of age. The younger sister presented at 7 weeks of age with generalized hypotonia. Both had normal CK levels. Both siblings were progressively microcephalic. PMID: 10642602 - 2 chet siblings with hypotonia within the first year of life. Both had elevated CK. Both siblings were progressively microcephalic PMID: 10642597 - 2 unrelated patients. One had profound hypotonia at 3 years of age. The other patient was markedly hypotonic in infancy. Both were microcephalic and hd elevated CK levels.; to: PMID: 16641202 - 2 siblings of consanguineous parents. One patient showed retarded motor skills at 1, 2 and 4 years old, with distal myopathy present at 3 years of age. The younger sister presented at 7 weeks of age with generalized hypotonia. Both had normal CK levels. Both siblings were progressively microcephalic. PMID: 10642602 - 2 chet siblings with hypotonia within the first year of life. Both had elevated CK. Both siblings were progressively microcephalic PMID: 10642597 - 2 unrelated patients. One had profound hypotonia at 3 years of age. The other patient was markedly hypotonic in infancy. Both were microcephalic and hd elevated CK levels. Contractures also reported. |
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| Fetal anomalies v0.1065 | DNAI1 | Zornitza Stark Phenotypes for gene: DNAI1 were changed from Primary ciliary dyskinesia 244400 to Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1063 | DNAH9 | Zornitza Stark Phenotypes for gene: DNAH9 were changed from Motile Cilia Defects and Situs Inversus to Ciliary dyskinesia, primary, 40, MIM# 618300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1062 | DNAH5 | Zornitza Stark Phenotypes for gene: DNAH5 were changed from CILIARY DYSKINESIA, PRIMARY, 3; Primary ciliary dyskinesia 608644; heterotaxy to Ciliary dyskinesia, primary, 3, with or without situs inversus (MIM #608644); Heterotaxy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1017 | DNAH8 | Seb Lunke Phenotypes for gene: DNAH8 were changed from Spermatogenic failure 46 - OMIM# 619095; primary ciliary dyskinesia to primary ciliary dyskinesia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1012 | DNAH1 | Seb Lunke Phenotypes for gene: DNAH1 were changed from Situs inversus; primary ciliary dyskinesia; infertility to Situs inversus; primary ciliary dyskinesia, MIM#617577; infertility, MIM#617576 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.985 | BRWD1 | Zornitza Stark reviewed gene: BRWD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Situs inversus, primary ciliary dyskinesia like; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.965 | NEK10 |
Krithika Murali gene: NEK10 was added gene: NEK10 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: NEK10 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEK10 were set to 31959991 Phenotypes for gene: NEK10 were set to Ciliary dyskinesia, primary, 44 - MIM#618781 Review for gene: NEK10 was set to RED Added comment: Nine individuals from 5 unrelated families with primary ciliary dyskinesia, some functional data. No features that can be ascertained antenatally reported. Sources: Literature |
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| Fetal anomalies v0.957 | MCIDAS |
Krithika Murali gene: MCIDAS was added gene: MCIDAS was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MCIDAS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MCIDAS were set to 32802948; 25048963; 30237576 Phenotypes for gene: MCIDAS were set to Hydrocephalus; Arachnoid cyst; Choroid plexus hyperplasia; Ciliary dyskinesia, primary, 42 - #618695 Review for gene: MCIDAS was set to GREEN Added comment: PMID 30237576 - Patient 17-1170 (Supplementary Table) Homozygous splice site variant in a child with progressive bronchiectasis, short stature and non-obstructive hydrocephalus on imaging. PMID 25048963 - 3 different homozygous variants reported in 4 unrelated families. Situs invertus not observed in any of the 9 individuals reported. Functional studies showed reduction of cilia. None of the variants identified were observed in gnomAD at unexpected frequency for a recessive condition. PMID 32802948 - Retrospective cohort study for 7 consecutive patients diagnosed with MCIDAS by the Leicester UK national PCD diagnostic laboratory. MRI-B showed that all 7 patients demonstrated choroid plexus hyperplasia, arachnoid cysts, hydrocephalus. x1 diagnosed antenatally with communicating hydrocephalus with a sibling who had increasing head circumference noted in infancy and baseline ultrasound scan showing CPH with bitempoeral arachnoid cysts. Another monozygotic twin from an unrelated family had seizures which self-resolved with D7 of life cranial U/S reported as within normal limits although mild dilatation of posterior horns of both lateral ventricles were noted. Both MZ twins had hydrocephalus diagnosed on MRI-B age 16 pre-lung transplant. Potential for younger age of ascertainment with earlier use of MRI-B. Sources: Literature |
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| Fetal anomalies v0.957 | GAS2L2 |
Krithika Murali gene: GAS2L2 was added gene: GAS2L2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: GAS2L2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GAS2L2 were set to 30665704 Phenotypes for gene: GAS2L2 were set to ?Ciliary dyskinesia, primary, 41 - OMIM#618449 Review for gene: GAS2L2 was set to RED Added comment: Two families with PCD and functional evidence. No mention of heterotaxy or phenotype that can be ascertained antenatally. Sources: Literature |
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| Fetal anomalies v0.957 | DNAJB13 |
Krithika Murali gene: DNAJB13 was added gene: DNAJB13 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: DNAJB13 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAJB13 were set to 31342671; 27486783 Phenotypes for gene: DNAJB13 were set to Primary ciliary dyskinesia Review for gene: DNAJB13 was set to RED Added comment: Two families reported with PCD phenotype, but no mention of heterotaxy. Sources: Literature |
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| Fetal anomalies v0.957 | DNAH8 |
Krithika Murali gene: DNAH8 was added gene: DNAH8 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: DNAH8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH8 were set to 31178125; 24307375; 32619401; 32681648 Phenotypes for gene: DNAH8 were set to Spermatogenic failure 46 - OMIM# 619095; primary ciliary dyskinesia Review for gene: DNAH8 was set to RED Added comment: Associated with male infertility, primary ciliary dyskinesia - no fetal phenotype reported Sources: Literature |
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| Fetal anomalies v0.957 | BRWD1 | Krithika Murali reviewed gene: BRWD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33389130; Phenotypes: Situs inversus, primary ciliary dyskinesia like; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.957 | DNAH1 |
Krithika Murali gene: DNAH1 was added gene: DNAH1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: DNAH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNAH1 were set to 25927852; 31507630 Phenotypes for gene: DNAH1 were set to Situs inversus; primary ciliary dyskinesia; infertility Review for gene: DNAH1 was set to AMBER Added comment: PMID - 25927852 x2 siblings from consanguineous Saudi family with homozygous missense variants (p.Lys1154Gln). More detailed clinical information available for proband diagnosed with Kartagener syndrome - chronic respiratory infections, situs inversus and infertility. Sister also reported to have been diagnosed with Kartagener syndrome at a similar age but no additional clinical information provided. PMID: 31765523 - 1 patient with PCD with a single het missense. PMID: 24360805 - 7 patients (4 different variants) with homozygous variants and infertility due to defective sperm. Microscopy of sperm revealed dynein disorganization PMID: 31507630 - 1 chet patient with kartagener syndrome, a subtype of PCD. Variants were classified as VUS initially - now c.442C>T (p.Arg148Cys) remains VUS, c.3103C > T p.R1035C re-classified as likely benign. Additional patient was het for a single nonsense, authors acknowledge missed 2nd hit and that this alone was not causative. Currently listed as red gene in Heterotaxy panel Sources: Literature |
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| Fetal anomalies v0.957 | CFAP74 |
Krithika Murali gene: CFAP74 was added gene: CFAP74 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP74 were set to 32555313 Phenotypes for gene: CFAP74 were set to infertility; primary ciliary dyskinesia Review for gene: CFAP74 was set to RED Added comment: Compound het missense variants identified in 2 unrelated patients presenting with male infertility, chronic bronchiectasis and frequent sinusitis. Sources: Literature |
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| Fetal anomalies v0.957 | CFAP57 |
Krithika Murali gene: CFAP57 was added gene: CFAP57 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: CFAP57 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: CFAP57 were set to 21574244; 32764743 Phenotypes for gene: CFAP57 were set to Van der Woude syndrome; primary ciliary dyskinesia like Review for gene: CFAP57 was set to RED Added comment: Homozygous nonsense variants identified in a 38-year-old male with PCD phenotype (history of neonatal respiratory distress, otitis media, sinusitis and bronchiectasis) x1 Het VUS reported in an individual with van der Woude syndrome - reviewed ClinVar - remains classified as VUS Sources: Literature |
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| Fetal anomalies v0.957 | BRWD1 |
Krithika Murali gene: BRWD1 was added gene: BRWD1 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: BRWD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BRWD1 were set to 33389130 Phenotypes for gene: BRWD1 were set to Situs inversus; primary ciliary dyskinesia like Review for gene: BRWD1 was set to GREEN Added comment: Biallelic missense variants reported in 3 unrelated individuals. Apart from asthenoteratozoospermia, all 3 had PCD or "PCD-likely" symptoms of re-occurring airway infections, bronchiectasis, and rhinosinusitis. One individual had situs inversus. Studies on cells from one indivdidual showed abnormal respiratory cilia structure. BRWD1 staining was absent from respiratory cilia in this individual (present in controls). Sources: Expert list, Literature |
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| Fetal anomalies v0.923 | CSF1R |
Zornitza Stark gene: CSF1R was added gene: CSF1R was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: CSF1R was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CSF1R were set to 30982609; 33749994; 34135456 Phenotypes for gene: CSF1R were set to Brain abnormalities, neurodegeneration, and dysosteosclerosis, MIM# 618476; BANDDOS Review for gene: CSF1R was set to GREEN Added comment: Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) is an autosomal recessive disorder characterized by brain abnormalities, progressive neurologic deterioration, and sclerotic bone dysplasia similar to dysosteosclerosis (DOS). The age at onset is highly variable: some patients may present in infancy with hydrocephalus, global developmental delay, and hypotonia, whereas others may have onset of symptoms in the late teens or early twenties after normal development. Neurologic features include loss of previous motor and language skills, cognitive impairment, spasticity, and focal seizures. Brain imaging shows periventricular white matter abnormalities and calcifications, large cisterna magna or Dandy-Walker malformation, and sometimes agenesis of the corpus callosum. Four unrelated families reported. Note mono-allelic variants cause an adult-onset disorder. Sources: Literature |
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| Fetal anomalies v0.886 | FOXJ1 |
Krithika Murali gene: FOXJ1 was added gene: FOXJ1 was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: FOXJ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOXJ1 were set to 31630787 Phenotypes for gene: FOXJ1 were set to Ciliary dyskinesia, primary, 43 - MIM# 618699 Review for gene: FOXJ1 was set to GREEN Added comment: Six unrelated individuals with de novo variants in this gene associated with a motile ciliopathy characterized by hydrocephalus, chronic destructive airway disease, and randomization of left/right body asymmetry Sources: Expert list, Literature |
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| Fetal anomalies v0.883 | DNAH11 | Zornitza Stark Phenotypes for gene: DNAH11 were changed from Primary ciliary dyskinesia 611884 to Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.881 | DNAAF4 | Zornitza Stark Phenotypes for gene: DNAAF4 were changed from PRIMARY CILIARY DYSPLASIA to Ciliary dyskinesia, primary, 25, MIM# 615482 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.879 | DNAAF3 | Zornitza Stark Phenotypes for gene: DNAAF3 were changed from PRIMARY CILIARY DYSKINEASIA; Ciliary dyskinesia, primary, 2, MIM:606763 to Ciliary dyskinesia, primary, 2, MIM# 606763 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.877 | DNAAF1 | Zornitza Stark Phenotypes for gene: DNAAF1 were changed from Primary ciliary dyskinesia 613193 to Ciliary dyskinesia, primary, 13, MIM# 613193 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.774 | ELOVL4 |
Belinda Chong changed review comment from: OMIM 614457: ISQMR is a severe autosomal recessive disorder characterised by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. 5 unrelated families reported, seizures in at least 4 of the families. OMIM 133190: Skin lesion appear shortly after birth and tend to disappear in young adulthood. In a large French-Canadian family, 14/19 individuals with a missense variant presented with erythrokeratodermia variabilis (PMID:24566826). At least two other individuals reported with erythrokeratodermia (and SCA34) as a result of a missense variant (PMID:26258735; 30065956). OMIM 600110: Stargardt disease-3 (STGD3) is an autosomal dominant juvenile macular dystrophy with onset most commonly in the second decade of life. Fundus examination reveals macular pigmentary changes and yellow flecks. Fluorescein angiography shows macular retinal pigment epithelium (RPE) defects; to: OMIM 614457: ISQMR is a severe autosomal recessive disorder characterised by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. 5 unrelated families reported, seizures in at least 4 of the families. OMIM 133190: Skin lesion appear shortly after birth and tend to disappear in young adulthood. In a large French-Canadian family, 14/19 individuals with a missense variant presented with erythrokeratodermia variabilis (PMID:24566826). At least two other individuals reported with erythrokeratodermia (and SCA34) as a result of a missense variant (PMID:26258735; 30065956). OMIM 600110: Stargardt disease-3 (STGD3) is an autosomal dominant juvenile macular dystrophy with onset most commonly in the second decade of life. Fundus examination reveals macular pigmentary changes and yellow flecks. Fluorescein angiography shows macular retinal pigment epithelium (RPE) defects |
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| Fetal anomalies v0.720 | CTC1 |
Zornitza Stark edited their review of gene: CTC1: Added comment: Cerebroretinal microangiopathy with calcifications and cysts (CRMCC), also known as Coats plus syndrome, is an autosomal recessive pleomorphic disorder characterized primarily by intracranial calcifications, leukodystrophy, and brain cysts, resulting in spasticity, ataxia, dystonia, seizures, and cognitive decline. Patients also have retinal telangiectasia and exudates (Coats disease) as well as extraneurologic manifestations, including osteopenia with poor bone healing and a high risk of gastrointestinal bleeding and portal hypertension caused by vasculature ectasias in the stomach, small intestine, and liver. Some individuals also have hair, skin, and nail changes, as well as anaemia and thrombocytopaenia. Multiple families reported.; Changed rating: GREEN; Changed publications: 22267198 |
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| Fetal anomalies v0.603 | COX7B | Zornitza Stark Phenotypes for gene: COX7B were changed from MICROPHTHALMIA WITH LINEAR SKIN LESIONS to Linear skin defects with multiple congenital anomalies 2, MIM#300887 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.542 | DSP | Zornitza Stark Phenotypes for gene: DSP were changed from Arrhythmogenic right ventricular dysplasia 8 607450; Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis 615821; Skin fragility-woolly hair syndrome 607655; Epidermolysis bullosa, lethal acantholytic 609638; Cardiomyopathy, dilated, with woolly hair and keratoderma 605676; Keratosis palmoplantaris striata II, 612908 to Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis, MIM# 615821; Cardiomyopathy, dilated, with woolly hair and keratoderma, MIM# 605676; Epidermolysis bullosa, lethal acantholytic, MIM# 609638 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.448 | ITGA6 |
Ain Roesley changed review comment from: At least 4 probands reported Pyelonephrosis, Urethrovesical occlusion and Stenosis at the ureterovesical junctions are some other features in this condition; to: At least 4 probands reported Epidermolysis bullosa with pyloric atresia (EB-PA) is characterized by fragility of the skin and mucous membranes, manifested by blistering with little or no trauma; congenital pyloric atresia; and ureteral and renal anomalies (dysplastic/multicystic kidney, hydronephrosis/hydroureter, ureterocele, duplicated renal collecting system, absent bladder). |
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| Fetal anomalies v0.388 | CCDC40 | Zornitza Stark Phenotypes for gene: CCDC40 were changed from CILIARY DYSKINESIA, PRIMARY, 15 to Ciliary dyskinesia, primary, 15, MIM#613808 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.386 | CCDC39 | Zornitza Stark Phenotypes for gene: CCDC39 were changed from CILIARY DYSKINESIA, PRIMARY, 14 to Ciliary dyskinesia, primary, 14, MIM# 613807 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.384 | CCDC114 | Zornitza Stark Phenotypes for gene: CCDC114 were changed from PRIMARY CILIARY DYSKINESIA to Ciliary dyskinesia, primary, 20, MIM# 615067 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.382 | CCDC103 | Zornitza Stark Phenotypes for gene: CCDC103 were changed from PRIMARY CILIARY DYSKINESIA to Ciliary dyskinesia, primary, 17, MIM# 614679 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.371 | CACNA1E | Zornitza Stark Phenotypes for gene: CACNA1E were changed from Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesia; Developmental and Epileptic Encephalopathy with Contractures Macrocephaly and Dyskinesias to Epileptic encephalopathy, early infantile, 69, MIM#618285 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.351 | C11orf70 | Zornitza Stark Phenotypes for gene: C11orf70 were changed from PRIMARY CILIARY DYSKINESIA to Ciliary dyskinesia, primary, 38, MIM# 618063 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.208 | ATP6V0A2 | Zornitza Stark Phenotypes for gene: ATP6V0A2 were changed from Cutis laxa, autosomal recessive, type IIA; Wrinkly skin syndrome 219200 to Cutis laxa, autosomal recessive, type IIA, MIM# 219200; Wrinkly skin syndrome, MIM#278250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.175 | ARMC4 | Zornitza Stark Phenotypes for gene: ARMC4 were changed from CILIARY DYSKINESIA, PRIMARY, 23 to Ciliary dyskinesia, primary, 23, MIM# 615451 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.84 | ALDH18A1 | Zornitza Stark Phenotypes for gene: ALDH18A1 were changed from SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT; MENTAL RETARDATION-JOINT HYPERMOBILITY-SKIN LAXITY WITH OR WITHOUT METABOLIC ABNORMALITIES; CUTIS LAXA, AUTOSOMAL DOMINANT 3 to Cutis laxa, autosomal dominant 3, MIM# 616603; Cutis laxa, autosomal recessive, type IIIA, MIM# 219150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.48 | ADAMTSL2 | Zornitza Stark changed review comment from: Variants in this gene cause a multi-system disorder involving the skeleton, skin, joints, and heart; however, theres is little evidence of intellectual disability in this disorder.; to: Variants in this gene cause a multi-system disorder involving the skeleton, skin, joints, and heart; perinatal presentation with skeletal and heart features reported. Multiple families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | SKIV2L |
Zornitza Stark gene: SKIV2L was added gene: SKIV2L was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: SKIV2L was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SKIV2L were set to TRICHOHEPATOENTERIC SYNDROME 2 |
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| Fetal anomalies v0.0 | RSPH3 |
Zornitza Stark gene: RSPH3 was added gene: RSPH3 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: RSPH3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RSPH3 were set to 30166424 Phenotypes for gene: RSPH3 were set to PRIMARY CILIARY DYSKINESIA WITH CENTRAL-COMPLEX DEFECTS |
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| Fetal anomalies v0.0 | RSPH1 |
Zornitza Stark gene: RSPH1 was added gene: RSPH1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: RSPH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RSPH1 were set to 30166424 Phenotypes for gene: RSPH1 were set to PRIMARY CILIARY DYSKINESIA WITH CENTRAL-COMPLEX AND RADIAL-SPOKE DEFECTS |
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| Fetal anomalies v0.0 | HYDIN |
Zornitza Stark gene: HYDIN was added gene: HYDIN was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: HYDIN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HYDIN were set to 30712880 Phenotypes for gene: HYDIN were set to CILIARY DYSKINESIA, PRIMARY, 5 |
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| Fetal anomalies v0.0 | GAS8 |
Zornitza Stark gene: GAS8 was added gene: GAS8 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: GAS8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GAS8 were set to 30166424 Phenotypes for gene: GAS8 were set to PRIMARY CILIARY DYSKINESIA |
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| Fetal anomalies v0.0 | CCNO |
Zornitza Stark gene: CCNO was added gene: CCNO was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: CCNO was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCNO were set to 30166424 Phenotypes for gene: CCNO were set to CILIARY DYSKINESIA, PRIMARY, 29 |
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| Fetal anomalies v0.0 | CCDC65 |
Zornitza Stark gene: CCDC65 was added gene: CCDC65 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: CCDC65 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC65 were set to 30166424 Phenotypes for gene: CCDC65 were set to PRIMARY CILIARY DYSKINESIA |
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| Fetal anomalies v0.0 | ZMYND10 |
Zornitza Stark gene: ZMYND10 was added gene: ZMYND10 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: ZMYND10 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ZMYND10 were set to PRIMARY CILIARY DYSKINESIA-22 |
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| Fetal anomalies v0.0 | TTC25 |
Zornitza Stark gene: TTC25 was added gene: TTC25 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: TTC25 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TTC25 were set to Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization |
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| Fetal anomalies v0.0 | RSPH9 |
Zornitza Stark gene: RSPH9 was added gene: RSPH9 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: RSPH9 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RSPH9 were set to Ciliary dyskinesia, primary 612650 |
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| Fetal anomalies v0.0 | RSPH4A |
Zornitza Stark gene: RSPH4A was added gene: RSPH4A was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: RSPH4A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RSPH4A were set to Ciliary dyskinesia, primary 612649 |
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| Fetal anomalies v0.0 | RIN2 |
Zornitza Stark gene: RIN2 was added gene: RIN2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: RIN2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RIN2 were set to MACROCEPHALY, ALOPECIA, CUTIS LAXA, AND SCOLIOSIS TALL FOREHEAD, SPARSE HAIR, SKIN HYPEREXTENSIBILITY, AND SCOLIOSIS |
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| Fetal anomalies v0.0 | PIH1D3 |
Zornitza Stark gene: PIH1D3 was added gene: PIH1D3 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: PIH1D3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PIH1D3 were set to Ciliary dyskinesia, primary, 36, X-linked, OMIM:300991; Ciliary dyskinesia, primary, 36, X-linked, MONDO:0010517 |
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| Fetal anomalies v0.0 | NDUFB11 |
Zornitza Stark gene: NDUFB11 was added gene: NDUFB11 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: NDUFB11 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: NDUFB11 were set to MICROPHTHALMIA WITH LINEAR SKIN DEFECTS SYNDROME |
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| Fetal anomalies v0.0 | LRRC56 |
Zornitza Stark gene: LRRC56 was added gene: LRRC56 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC56 were set to 30388400 Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39, OMIM:618254; Ciliary dyskinesia, primary, 39, MONDO:0032637 |
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| Fetal anomalies v0.0 | EXPH5 |
Zornitza Stark gene: EXPH5 was added gene: EXPH5 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: EXPH5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EXPH5 were set to INHERITED SKIN FRAGILITY |
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| Fetal anomalies v0.0 | DRC1 |
Zornitza Stark gene: DRC1 was added gene: DRC1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: DRC1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DRC1 were set to PRIMARY CILARY DYSKINEASIA |
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| Fetal anomalies v0.0 | DNAL1 |
Zornitza Stark gene: DNAL1 was added gene: DNAL1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: DNAL1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAL1 were set to Ciliary dyskinesia, primary, 16, 614017 |
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| Fetal anomalies v0.0 | DNAI2 |
Zornitza Stark gene: DNAI2 was added gene: DNAI2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: DNAI2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAI2 were set to Ciliary dyskinesia, primary, 9, with or without situs inversus,612444 |
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| Fetal anomalies v0.0 | DNAAF5 |
Zornitza Stark gene: DNAAF5 was added gene: DNAAF5 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: DNAAF5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAAF5 were set to Primary ciliary dyskinesia 18, MONDO:0013940; Ciliary dyskinesia, primary, 18, OMIM:614874 |
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| Fetal anomalies v0.0 | DNAAF2 |
Zornitza Stark gene: DNAAF2 was added gene: DNAAF2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: DNAAF2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAAF2 were set to Ciliary dyskinesia, primary, 10, 612518 |
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| Fetal anomalies v0.0 | CCDC151 |
Zornitza Stark gene: CCDC151 was added gene: CCDC151 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: CCDC151 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CCDC151 were set to Primary ciliary dyskinesia 30, MONDO:0014465; Ciliary dyskinesia, primary, 30, OMIM:616037 |
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| Fetal anomalies v0.0 | C21orf59 |
Zornitza Stark gene: C21orf59 was added gene: C21orf59 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: C21orf59 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: C21orf59 were set to Primary ciliary dyskinesia 26, MONDO:0014211; Ciliary dyskinesia, primary, 26, OMIM:615500 |
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| Fetal anomalies v0.0 | TUBB |
Zornitza Stark gene: TUBB was added gene: TUBB was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: TUBB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TUBB were set to CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 6; Circumferential Skin Creases Kunze Type |
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| Fetal anomalies v0.0 | TRPV4 |
Zornitza Stark gene: TRPV4 was added gene: TRPV4 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: TRPV4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TRPV4 were set to METATROPIC DYSPLASIA; SPONDYLOMETAPHYSEAL DYSPLASIA, KOZLOWSKI TYPE |
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| Fetal anomalies v0.0 | TRIP4 |
Zornitza Stark gene: TRIP4 was added gene: TRIP4 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: TRIP4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRIP4 were set to 26924529; 27008887 Phenotypes for gene: TRIP4 were set to Prenatal-onset spinal muscular atrophy with congenital bone fractures, MONDO:0000209; Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, MONDO:0014896; ?Muscular dystrophy, congenital, Davignon-Chauveau type, OMIM:617066; Spinal muscular atrophy with congenital bone fractures 1, OMIM:616866; Spinal muscular atrophy with congenital bone fractures 1, MONDO:0014806 |
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| Fetal anomalies v0.0 | TCTN3 |
Zornitza Stark gene: TCTN3 was added gene: TCTN3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: TCTN3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TCTN3 were set to MOHR-MAJEWSKI SYNDROME |
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| Fetal anomalies v0.0 | SPAG1 |
Zornitza Stark gene: SPAG1 was added gene: SPAG1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: SPAG1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SPAG1 were set to PRIMARY CILIARY DYSKINESIA ASSOCIATED WITH DEFECTIVE OUTER AND INNER DYNEIN ARMS. |
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| Fetal anomalies v0.0 | SKI |
Zornitza Stark gene: SKI was added gene: SKI was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: SKI was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SKI were set to SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME |
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| Fetal anomalies v0.0 | PTDSS1 |
Zornitza Stark gene: PTDSS1 was added gene: PTDSS1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: PTDSS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: PTDSS1 were set to LENZ-MAJEWSKI HYPEROSTOTIC DWARFISM |
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| Fetal anomalies v0.0 | MAPRE2 |
Zornitza Stark gene: MAPRE2 was added gene: MAPRE2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: MAPRE2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: MAPRE2 were set to 31903734; 31502381; 26637975 Phenotypes for gene: MAPRE2 were set to Symmetric circumferential skin creases, congenital, 2, 616734 |
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| Fetal anomalies v0.0 | LRRC6 |
Zornitza Stark gene: LRRC6 was added gene: LRRC6 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: LRRC6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LRRC6 were set to PRIMARY CILIARY DISKINESIA |
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| Fetal anomalies v0.0 | LMNA |
Zornitza Stark gene: LMNA was added gene: LMNA was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: LMNA was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: LMNA were set to LETHAL TIGHT SKIN CONTRACTURE SYNDROME; CARDIOMYOPATHY DILATED WITH HYPERGONADOTROPIC HYPOGONADISM; FAMILIAL PARTIAL LIPODYSTROPHY TYPE 2; HUTCHINSON-GILFORD PROGERIA SYNDROME; EMERY-DREIFUSS MUSCULAR DYSTROPHY TYPE 2; MUSCULAR DYSTROPHY CONGENITAL LMNA-RELATED; CHARCOT-MARIE-TOOTH DISEASE TYPE 2B1; MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY; HEART-HAND SYNDROME SLOVENIAN TYPE; CARDIOMYOPATHY DILATED TYPE 1A; LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 1B |
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| Fetal anomalies v0.0 | DSP |
Zornitza Stark gene: DSP was added gene: DSP was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: DSP was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: DSP were set to 30993396 Phenotypes for gene: DSP were set to Arrhythmogenic right ventricular dysplasia 8 607450; Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis 615821; Skin fragility-woolly hair syndrome 607655; Epidermolysis bullosa, lethal acantholytic 609638; Cardiomyopathy, dilated, with woolly hair and keratoderma 605676; Keratosis palmoplantaris striata II, 612908 |
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| Fetal anomalies v0.0 | DNAI1 |
Zornitza Stark gene: DNAI1 was added gene: DNAI1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: DNAI1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAI1 were set to Primary ciliary dyskinesia 244400 |
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| Fetal anomalies v0.0 | DNAH5 |
Zornitza Stark gene: DNAH5 was added gene: DNAH5 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: DNAH5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAH5 were set to CILIARY DYSKINESIA, PRIMARY, 3; Primary ciliary dyskinesia 608644; heterotaxy |
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| Fetal anomalies v0.0 | DNAH11 |
Zornitza Stark gene: DNAH11 was added gene: DNAH11 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: DNAH11 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAH11 were set to Primary ciliary dyskinesia 611884 |
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| Fetal anomalies v0.0 | DNAAF3 |
Zornitza Stark gene: DNAAF3 was added gene: DNAAF3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: DNAAF3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAAF3 were set to PRIMARY CILIARY DYSKINEASIA; Ciliary dyskinesia, primary, 2, MIM:606763 |
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| Fetal anomalies v0.0 | DNAAF1 |
Zornitza Stark gene: DNAAF1 was added gene: DNAAF1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: DNAAF1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAAF1 were set to Primary ciliary dyskinesia 613193 |
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| Fetal anomalies v0.0 | COX7B |
Zornitza Stark gene: COX7B was added gene: COX7B was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: COX7B was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: COX7B were set to MICROPHTHALMIA WITH LINEAR SKIN LESIONS |
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| Fetal anomalies v0.0 | CCDC40 |
Zornitza Stark gene: CCDC40 was added gene: CCDC40 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CCDC40 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CCDC40 were set to CILIARY DYSKINESIA, PRIMARY, 15 |
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| Fetal anomalies v0.0 | CCDC39 |
Zornitza Stark gene: CCDC39 was added gene: CCDC39 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CCDC39 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CCDC39 were set to CILIARY DYSKINESIA, PRIMARY, 14 |
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| Fetal anomalies v0.0 | CCDC114 |
Zornitza Stark gene: CCDC114 was added gene: CCDC114 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CCDC114 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CCDC114 were set to PRIMARY CILIARY DYSKINESIA |
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| Fetal anomalies v0.0 | CCDC103 |
Zornitza Stark gene: CCDC103 was added gene: CCDC103 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CCDC103 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CCDC103 were set to PRIMARY CILIARY DYSKINESIA |
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| Fetal anomalies v0.0 | CACNA1E |
Zornitza Stark gene: CACNA1E was added gene: CACNA1E was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CACNA1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CACNA1E were set to 30849329 Phenotypes for gene: CACNA1E were set to Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesia; Developmental and Epileptic Encephalopathy with Contractures Macrocephaly and Dyskinesias Mode of pathogenicity for gene: CACNA1E was set to Other - please provide details in the comments |
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| Fetal anomalies v0.0 | C11orf70 |
Zornitza Stark gene: C11orf70 was added gene: C11orf70 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: C11orf70 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C11orf70 were set to 29727692; 29727693 Phenotypes for gene: C11orf70 were set to PRIMARY CILIARY DYSKINESIA |
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| Fetal anomalies v0.0 | ATP6V0A2 |
Zornitza Stark gene: ATP6V0A2 was added gene: ATP6V0A2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ATP6V0A2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ATP6V0A2 were set to Cutis laxa, autosomal recessive, type IIA; Wrinkly skin syndrome 219200 |
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| Fetal anomalies v0.0 | ARMC4 |
Zornitza Stark gene: ARMC4 was added gene: ARMC4 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ARMC4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ARMC4 were set to CILIARY DYSKINESIA, PRIMARY, 23 |
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| Fetal anomalies v0.0 | ALDH18A1 |
Zornitza Stark gene: ALDH18A1 was added gene: ALDH18A1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ALDH18A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: ALDH18A1 were set to SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT; MENTAL RETARDATION-JOINT HYPERMOBILITY-SKIN LAXITY WITH OR WITHOUT METABOLIC ABNORMALITIES; CUTIS LAXA, AUTOSOMAL DOMINANT 3 |
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