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Intellectual disability - microarray and sequencing v3.1525 | ACTL6B | Arina Puzriakova Phenotypes for gene: ACTL6B were changed from Global developmental delay; Intellectual disability to Developmental and epileptic encephalopathy 76, OMIM:618468; Intellectual developmental disorder with severe speech and ambulation defects, OMIM:618470 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.846 | ACTL6B | Rebecca Foulger Classified gene: ACTL6B as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.846 | ACTL6B | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green based on recent review by Konstantinos Varvagiannis which provides additional recent cases from PMIDs:31031012,30656450,26539891 and 30237576. Sufficient unrelated cases with a consistent ID/global developmental delay phenotype to support inclusion on the panel. Plus functional studies in human and mouse cells in PMIDs:31031012,17920018. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.846 | ACTL6B | Rebecca Foulger Gene: actl6b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.845 | ACTL6B |
Rebecca Foulger commented on gene: ACTL6B: Karaca et al, 2015 (PMID:26539891) report a homozygous variant (NM_016188: c.G893A; p.R298Q) in two siblings BAB6569 and BAB6570 with severe ID, microcephaly, seizures and some autistic behavioral pattern (BAB6570 appears in the text but not table 1). Sajan et al., 2017 (PMID:27171548) report a homozygous stoploss variant in ACTL6B: c.1279delT (p.X427D) in an ASD case from the DDD study (PMID:25533962) but no other clinical or EEG data was provided. Maddirevula et al 2019 (PMID:30237576) searched their database on exomes in search of homozygous variants that could be linked to diseases. They identified the homozygous variant NM_016188.4:c.999T>A:p.(Cys333*) in a 13 year old girl (individual 17-1447) with phenotype global developmental delay, vs hyperekplexia, and basal ganglia abnormalities. |
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Intellectual disability - microarray and sequencing v2.845 | ACTL6B | Rebecca Foulger commented on gene: ACTL6B: Bell et al., 2019 (PMID:31031012) identified 11 individuals (from 10 families) with biallelic variants in ACTL6B and global developmental delay, epileptic encephalopathy, and spasticity. They also identified 10 unrelated individuals with de novo heterozygous variants with ID, developmental delay, hypotonia, Rett-like stereotypies (e.g. handwringing), and minor facial dysmorphisms: 9/10 of these individuals had the identical de novo c.1027G>A (p.Gly343Arg) mutation. Engineered knock-out of ACTL6B in wild-type human neurons resulted in profound deficits in dendrite development. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.845 | ACTL6B | Rebecca Foulger Publications for gene: ACTL6B were set to 26350204 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.844 | ACTL6B | Rebecca Foulger Added comment: Comment on mode of inheritance: Most literature report biallelic ACTL6B variants in individuals with developmental delay/intellectual disability but Bell et al., 2019 (PMID:31031012) identify both biallelic and heterozygous variants. Therefore have set MOI to BOTH monoallelic and biallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.844 | ACTL6B | Rebecca Foulger Mode of inheritance for gene: ACTL6B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.843 | ACTL6B | Rebecca Foulger Added comment: Comment on mode of pathogenicity: Bell et al., 2019 (PMID:31031012) suggest that biallelic variants are loss-of-function, and heterozygous variants are gain-of-function. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.843 | ACTL6B | Rebecca Foulger Mode of pathogenicity for gene: ACTL6B was changed from to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.842 | ACTL6B | Rebecca Foulger Phenotypes for gene: ACTL6B were changed from to Global developmental delay; Intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.800 | ACTL6B | Konstantinos Varvagiannis reviewed gene: ACTL6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31031012, 30656450, 26539891, 27171548, 30237576; Phenotypes: Global developmental delay, Intellectual disability, Seizures, Spasticity, Global developmental delay, Intellectual disability, Stereotypic behavior, Abnormality of the face; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes |