Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
5 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.278 | ATOH1 | Ida Ertmanska changed review comment from: Comment on list classification: There are 4 individuals from 3 unrelated families reported in literature with biallelic ATOH1 variants and an associated neurodevelopmental syndrome. All patients presented with severe GDD/ID. Based on available evidence, this gene should be promoted to Green for Intellectual disability.; to: Comment on list classification: There are 4 individuals from 3 unrelated families reported in literature with biallelic ATOH1 variants and an associated neurodevelopmental syndrome. All patients presented with severe GDD/ID. Individuals with heterozygous ATOH1 variants present with hearing loss and mild cerebellar signs, without intellectual disability. Hene, based on available evidence, this gene should be promoted to Green for Intellectual disability with MOI set to BIALLELIC, autosomal or pseudoautosomal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.278 | ATOH1 | Ida Ertmanska Classified gene: ATOH1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.278 | ATOH1 | Ida Ertmanska Added comment: Comment on list classification: There are 4 individuals from 3 unrelated families reported in literature with biallelic ATOH1 variants and an associated neurodevelopmental syndrome. All patients presented with severe GDD/ID. Based on available evidence, this gene should be promoted to Green for Intellectual disability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.278 | ATOH1 | Ida Ertmanska Gene: atoh1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.277 | ATOH1 |
Ida Ertmanska gene: ATOH1 was added gene: ATOH1 was added to Intellectual disability. Sources: Literature Q1_26_promote_green tags were added to gene: ATOH1. Mode of inheritance for gene: ATOH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATOH1 were set to 9367153; 21146598; 33111345; 35518571; 41592563 Phenotypes for gene: ATOH1 were set to ?Deafness, autosomal dominant 89 , OMIM:620284; hearing loss, autosomal dominant 89, MONDO:0859528; pontocerebellar hypoplasia, MONDO:0020135 Review for gene: ATOH1 was set to GREEN Added comment: PMID: 41592563 Bertola et al., 2026 Report of 5 unrelated families with heterozygous frameshift variants in ATOH1 associated with hearing loss (7/7, mild to severe), cerebellar symptoms (4/6), and a pattern of brainstem malformations (7/7). Cerebellar symptoms are noted to be subtle: motor delay, balance issues, mild ataxia, tremor, and other cerebellar signs. Intellectual disability ascertained in 1/7 individuals - this patient also carried a RNU4-2 variant, thought to be responsible for ID in this case. Authors also report a homozygous early-truncating variant c.102dup, (p.Pro35AlafsTer18), causing a distinct neurodevelopmental syndrome with severe pontocerebellar hypoplasia, severe ID, and profound hearing loss. Heterozygous parents were asymptomatic. PMID: 35518571 Višnjar et al., 2022 A homozygous missense variant NM_005172.1:c.481C>G, p.(Arg161Gly) in the ATOH1 gene was identified in the proband and his affected sister, segregating with apparently recessive pontocerebellar hypoplasia (PCH), severe global developmental delay, intellectual disability, and hearing loss. Brain MRI findings were: posteriorly thin corpus callosum, small posterior fossa with the upward displacement of the tentorium, small cerebellum with more severely hypoplastic vermis than hemispheres, and small brainstem. PMID: 33111345 Brownstein et al., 2020 Family HL263: Mizrahi Jewish family, affected individuals heterozygous for ATOH1 c.1030delC, p.His344fs17Ter (affects C-terminus). Variant co-segregated over five generations with progressive non-syndromic hearing loss, with onset at birth or early childhood. Method: WES. Western analysis revealed a significantly slower rate of degradation for mutant ATOH1 protein compared to wild-type ATOH1. Increased protein stability = untimely expression leading to hearing loss. PMID: 27431290 Anazi et al., 2017 Cohort of ID patients. Patient 15DG1898 was homozygous for ATOH1: c.212del, p.(Gly71Alafs*36); clinical presentation: ID, generalised hypotonia, nystagmus, pontocerebellar hypoplasia, brain atrophy (frontal lobe). No mention of hearing loss (not assessed?). Functional evidence: Loss of Atoh1 in mice causes hearing impairment, cerebellar and cochlear malformations, and death (PMID: 9367153, Ben-Arie et al., 1997. ATOH1 previously known as MATH1). Conditional deletion of Atoh1 leads to lack of differentiated inner ear hair cells (PMID: 21146598 Pan et al., 2010). ATOH1 is putatively linked to ?Deafness, autosomal dominant 89, MIM:620284 in OMIM (accessed 23rd Feb 2026). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||