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| Ataxia and cerebellar anomalies - narrow panel v8.63 | ATOH1 | Ida Ertmanska Mode of inheritance for gene: ATOH1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.62 | ATOH1 | Ida Ertmanska edited their review of gene: ATOH1: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.62 | ATOH1 | Ida Ertmanska changed review comment from: Comment on list classification: There are 6 unrelated families with heterozygous ATOH1 variants, presenting with hearing loss. Subtle cerebellar symptoms were present in 4/6 patients. In addition, 4 individuals from 3 unrelated families have been reported with biallelic ATOH1 variants, presenting with pontocerebellar hypoplasia. Functional evidence from mouse models supports this gene-disease assiociation. Based on available evidence, this gene should be promoted to Green on Ataxia and cerebellar anomalies - narrow panel, with MOI set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal. ; to: Comment on list classification: There are 6 unrelated families with heterozygous ATOH1 variants, presenting with hearing loss. Subtle cerebellar symptoms were present in 4/6 patients. In addition, 4 individuals from 3 unrelated families have been reported with biallelic ATOH1 variants, presenting with pontocerebellar hypoplasia. Functional evidence from mouse models supports this gene-disease assiociation - atoh1-/- knockout mice lack cerebellar granule neurons. Based on available evidence, this gene should be promoted to Green on Ataxia and cerebellar anomalies - narrow panel, with MOI set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.62 | ATOH1 |
Ida Ertmanska changed review comment from: 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. Heterozygous variants detected: c.1030dup (p.His344ProfsTer6) - recurred de novo in 3 individuals; c.853-856dup (p.Ser286LeufsTer65); c.1053del (p.Asp351GlufsTer11). 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).; to: 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. Heterozygous variants detected: c.1030dup (p.His344ProfsTer6) - recurred de novo in 3 individuals; c.853-856dup (p.Ser286LeufsTer65); c.1053del (p.Asp351GlufsTer11). 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 a lack of cerebellar granule neurons, resulting in hearing impairment, cerebellar and cochlear malformations, and death (PMID: 9367153, Ben-Arie et al., 1997. ATOH1 previously known as MATH1). ATOH1 is putatively linked to ?Deafness, autosomal dominant 89, MIM:620284 in OMIM (accessed 23rd Feb 2026). |
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| Ataxia and cerebellar anomalies - narrow panel v8.62 | ATOH1 | Ida Ertmanska changed review comment from: Comment on list classification: There are 6 unrelated families with heterozygous ATOH1 variants, presenting with hearing loss (with or without a cerebellar disorder). 4 individuals from 3 unrelated families have been reported with biallelic ATOH1 variants, with pontocerebellar hypoplasia. Based on available evidence, this gene should be promoted to Green on Ataxia and cerebellar anomalies - narrow panel, with MOI set to BOTH; to: Comment on list classification: There are 6 unrelated families with heterozygous ATOH1 variants, presenting with hearing loss. Subtle cerebellar symptoms were present in 4/6 patients. In addition, 4 individuals from 3 unrelated families have been reported with biallelic ATOH1 variants, presenting with pontocerebellar hypoplasia. Functional evidence from mouse models supports this gene-disease assiociation. Based on available evidence, this gene should be promoted to Green on Ataxia and cerebellar anomalies - narrow panel, with MOI set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.62 | ATOH1 |
Ida Ertmanska changed review comment from: PMID: 41592563 Bertola et al., 2026 Report of 5 unrelated families with heterozygous frameshift variants in ATOH1 associated with hearing loss, subtle motor impairments, and a pattern of brainstem malformations. Authors also report a homozygous early-truncating variant, causing a distinct neurodevelopmental syndrome with highly severe cerebellar and pontine hypoplasia. PMID: 35518571 Višnjar et al., 2022 A homozygous missense variant (NM_005172.1:c.481C>G) 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: 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; to: 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. Heterozygous variants detected: c.1030dup (p.His344ProfsTer6) - recurred de novo in 3 individuals; c.853-856dup (p.Ser286LeufsTer65); c.1053del (p.Asp351GlufsTer11). 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). |
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| Ataxia and cerebellar anomalies - narrow panel v8.62 | ATOH1 | Ida Ertmanska Classified gene: ATOH1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.62 | ATOH1 | Ida Ertmanska Added comment: Comment on list classification: There are 6 unrelated families with heterozygous ATOH1 variants, presenting with hearing loss (with or without a cerebellar disorder). 4 individuals from 3 unrelated families have been reported with biallelic ATOH1 variants, with pontocerebellar hypoplasia. Based on available evidence, this gene should be promoted to Green on Ataxia and cerebellar anomalies - narrow panel, with MOI set to BOTH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.62 | ATOH1 | Ida Ertmanska Gene: atoh1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.61 | ATOH1 |
Ida Ertmanska gene: ATOH1 was added gene: ATOH1 was added to Ataxia and cerebellar anomalies - narrow panel. 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, subtle motor impairments, and a pattern of brainstem malformations. Authors also report a homozygous early-truncating variant, causing a distinct neurodevelopmental syndrome with highly severe cerebellar and pontine hypoplasia. PMID: 35518571 Višnjar et al., 2022 A homozygous missense variant (NM_005172.1:c.481C>G) 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: 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 |
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