Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous UCHL1 variants have been reported, including 13 heterozygous loss-of-function variants (15 families) and a heterozygous inframe insertion (3 families) in PMID: 35986737. These affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).; to: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous UCHL1 variants have been reported, including 13 heterozygous loss-of-function variants (15 families) and a heterozygous inframe insertion (3 families) in PMID: 35986737. The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).
Sarah Leigh edited their review of gene: UCHL1: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous UCHL1 variants have been reported, including 13 heterozygous loss-of-function variants (15 families) and a heterozygous inframe insertion (3 families) in PMID: 35986737. These affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sarah Leigh Added comment: Comment on mode of inheritance: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous loss of function UCHL1 variants.
Sarah Leigh Mode of inheritance for gene: UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Green - ataxia and other cerebellar signs are a feature of this UCHL1-related neurodegenerative disorder. At least 4 unrelated families reported (PMIDs: 23359680; 28007905; 29735986; 32656641) with different biallelic variants, supported by functional and animal model data.
Arina Puzriakova Phenotypes for gene: UCHL1 were changed from Early onset ataxia and optic neuropathy to Spastic paraplegia 79, autosomal recessive, OMIM:615491