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Intellectual disability syndromic and non-syndromic v0.5925 | THRA | Zornitza Stark Marked gene: THRA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability syndromic and non-syndromic v0.5925 | THRA | Zornitza Stark Gene: thra has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability syndromic and non-syndromic v0.5925 | THRA | Zornitza Stark Phenotypes for gene: THRA were changed from to Hypothyroidism congenital nongoitrous 6 (MIM 614450) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability syndromic and non-syndromic v0.5924 | THRA | Zornitza Stark Publications for gene: THRA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability syndromic and non-syndromic v0.5923 | THRA | Zornitza Stark Mode of inheritance for gene: THRA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability syndromic and non-syndromic v0.5881 | THRA |
Hnin Aung changed review comment from: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestation for truncating variants have been observed. Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938). Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].; to: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestations for truncating variants have been observed. Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938). Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899]. |
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Intellectual disability syndromic and non-syndromic v0.5881 | THRA |
Hnin Aung changed review comment from: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestation for truncating variants have been observed. Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938). Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].; to: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestation for truncating variants have been observed. Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938). Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899]. |
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Intellectual disability syndromic and non-syndromic v0.5881 | THRA | Hnin Aung reviewed gene: THRA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22494134, 23940126, 24847461, 25670821, 26037512, 25621899, 27144938, 28856816, 30842990, 37469961; Phenotypes: Hypothyroidism congenital nongoitrous 6 (MIM 614450), Intellectual disability syndromic, Growth retardation, Facial dysmorphism, Constipation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability syndromic and non-syndromic v0.0 | THRA |
Zornitza Stark gene: THRA was added gene: THRA was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland Mode of inheritance for gene: THRA was set to Unknown |