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| Intellectual disability syndromic and non-syndromic v0.6232 | EP300 | Bryony Thompson Marked gene: EP300 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.6232 | EP300 | Bryony Thompson Gene: ep300 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.6232 | EP300 | Bryony Thompson Phenotypes for gene: EP300 were changed from to Rubinstein-Taybi syndrome MONDO:0019188 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.6231 | EP300 | Bryony Thompson Publications for gene: EP300 were set to https://search.clinicalgenome.org/CCID:004751 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.6230 | EP300 | Bryony Thompson Publications for gene: EP300 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.6229 | EP300 | Bryony Thompson Mode of inheritance for gene: EP300 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.6222 | EP300 |
Ken Lee Wan changed review comment from: EP300 is definitively associated with autosomal dominant Rubinstein-Taybi syndrome. Rubinstein-Taybi syndrome is characterized by distinctive facial features, broad and angulated thumbs and halluces, short stature, and intellectual disability (https://search.clinicalgenome.org/CCID:004751). Mechanism of disease: loss of function; to: EP300 is definitively associated with autosomal dominant Rubinstein-Taybi syndrome. Rubinstein-Taybi syndrome is characterized by distinctive facial features, broad and angulated thumbs and halluces, short stature and intellectual disability (https://search.clinicalgenome.org/CCID:004751). Mechanism of disease: loss of function |
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| Intellectual disability syndromic and non-syndromic v0.6222 | EP300 | Ken Lee Wan reviewed gene: EP300: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rubinstein-Taybi syndrome MONDO:0019188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.2659 | TTC5 |
Konstantinos Varvagiannis gene: TTC5 was added gene: TTC5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTC5 were set to 29302074; 32439809 Phenotypes for gene: TTC5 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Microcephaly; Abnormality of the face; Behavioral abnormality; Abnormality of the genitourinary system Penetrance for gene: TTC5 were set to Complete Review for gene: TTC5 was set to GREEN Added comment: Hu et al (2019 - PMID: 29302074) reported briefly on 3 individuals from 2 consanguineous families (from Turkey and Iran) with biallelic TTC5 variants. Features included DD (3/3), ID (severe in 2/2 with relevant age), microcephaly (3/3), brain abnormalities, etc. A nonsense and a variant affecting splice site were identified by WES/WGS. --- In a recent report, Rasheed et al (2020 - PMID: 32439809) report on the phenotype of 8 individuals - belonging to 5 consanguineous families - all 8 harboring homozygous TTC5 mutations. Frequent features included hypotonia (6/8), motor and speech delay, moderate to severe ID (10/10 of relevant age - inclusion of less severely affected subjects was not considered by study design), brain MRI abnormalities (8/8). Other findings included microcephaly in some (6/11), behavioral abnormalities in few (autistic behavior in 2/8, aggression in 2/8), genitourinary anomalies (2/8), seizures (1/11). Facial phenotype incl. thin V-shaped upper lip, low-set ears (in most) and/or additional features. TTC5 encodes a 440 aa protein, functioning as a scaffold to stabilise p300-JMY interactions. Apart from this role in nucleus, it has functions in the cytoplasm (inhibiting actin nucleataion, autophagosome formation, etc). The gene has ubiquitous expression, highest in brain. All variants were identified following WES - as the best candidates - in affected individuals with compatible Sanger studies in all affected family members and carrier parents. 2 missense and 2 nonsense variants were identified with the 2 missense SNVs localizing within TPR domains. qRT-PCR studies for a nonsense variant localizing 19 nt before the last exon, revealed fourfold decreased expression in affected individuals compared to carriers. Families from Egypt shared a homozygous ~6.3 Mb haplotype block spanning TTC5, suggesting that p.(Arg263Ter) is likely a founder mutation. The authors underscore some phenotypic (though not facial) similarities with Rubinstein-Taybi syndrome 2 due to EP300 mutations (in line with the role of TTC5). Biallelic variants in genes encoding other members of the TTC family (containing a TPR motif), e.g. TTC8 or TTC15 cause disorders with neurologic manifestations (and DD/ID). Sources: Literature |
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| Intellectual disability syndromic and non-syndromic v0.0 | EP300 |
Zornitza Stark gene: EP300 was added gene: EP300 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland Mode of inheritance for gene: EP300 was set to Unknown |
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