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| Ataxia and cerebellar anomalies - narrow panel v4.59 | CAPRIN1 | Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Cerebellar ataxia, MONDO:0000437; Early-onset ataxia to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.1 | CAPRIN1 |
Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green. PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor & sensory axonal neuropathy) as the other two patients. In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics. These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green. PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor/ sensory axonal neuropathy) as the other two patients. In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics. These functional evidences also suggest a gain-of-function mechanism for P512L variant. |
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| Ataxia and cerebellar anomalies - narrow panel v4.1 | CAPRIN1 |
Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green. PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor > sensory axonal neuropathy) as the other two patients. In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics. These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green. PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor & sensory axonal neuropathy) as the other two patients. In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics. These functional evidences also suggest a gain-of-function mechanism for P512L variant. |
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| Ataxia and cerebellar anomalies - narrow panel v3.32 | CAPRIN1 | Achchuthan Shanmugasundram Phenotypes for gene: CAPRIN1 were changed from Infantile-onset ataxia to Cerebellar ataxia, MONDO:0000437; Early-onset ataxia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.31 | CAPRIN1 | Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.31 | CAPRIN1 | Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.30 | CAPRIN1 |
Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor > sensory axonal neuropathy) as the other two patients. In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics. These functional evidences also suggest a gain-of-function mechanism for P512L variant.; to: Comment on classification: This gene should be rated Amber as the two confirmed patients were identified with the same variant, despite additional functional evidence. The 'watchlist' tag has been added to look out for new evidence in order to promote this gene to green. PMID:36136249 reports two unrelated cases with early-onset ataxia – one with Turkish and another with Italian descent. Both harboured the same heterozygous variant c.1535C>T (p.Pro512Leu). The authors also mention that they were notified by GeneMatcher of a 14 years old female patient with exactly the same de-novo variant and an identical phenotype (cerebellar atrophy, ataxia and motor > sensory axonal neuropathy) as the other two patients. In silico analyses predict an increased aggregation propensity of the mutated protein. Overexpression of CAPRIN1 protein harbouring P512L variant forms insoluble aggregates and sequester ataxia-related proteins. CAPRIN1 with P512L variant in isogenic iPSC-derived cortical neurons causes reduced neuronal activity and altered stress granule dynamics. These functional evidences also suggest a gain-of-function mechanism for P512L variant. |
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| Ataxia and cerebellar anomalies - narrow panel v3.30 | CAPRIN1 | Achchuthan Shanmugasundram Tag watchlist tag was added to gene: CAPRIN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.30 | CAPRIN1 | Achchuthan Shanmugasundram reviewed gene: CAPRIN1: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 36136249; Phenotypes: Cerebellar ataxia, MONDO:0000437, Early-onset ataxia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v3.16 | CAPRIN1 |
Dmitrijs Rots gene: CAPRIN1 was added gene: CAPRIN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CAPRIN1 were set to 36136249 Phenotypes for gene: CAPRIN1 were set to Infantile-onset ataxia Penetrance for gene: CAPRIN1 were set to Complete Mode of pathogenicity for gene: CAPRIN1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: CAPRIN1 was set to GREEN Added comment: CAPRIN1 is reported in two indepedent cases with infantile-onset ataxia and cognitive decline (reported 2 de novo in two cases + functional evidence, so enough evidence for green rating). Sources: Literature |
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