Hereditary ataxia
Gene: XRCC1
Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team) it was agreed that there is enough evidence to promote this gene from Red to Green.
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Three individuals from unrelated families all from South Asian descent with cerebellar ataxia and peripheral neuropathy and a recurrent variant (c.1293G>C, 2 homozygotes and a comp het) in the XRCC1 gene. Homozygosity mapping in 2 families confirmed a shared haplotype and the recurrent variant is found in a heterozygous state in an unaffected sib and 4 individuals of South Asian descent in ExAC - indicating that this is a founder variant that is pathogenic when in trans with a second variant. There is some strong functional evidence that supports pathogenicity, including an animal model that recapitulated human phenotypes such as cerebellar ataxia.Created: 28 Jun 2021, 3:36 p.m. | Last Modified: 28 Jun 2021, 3:36 p.m.
Panel Version: 1.231
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633
Publications
New publication reporting compound heterozygous variant in the proband, whereas their unaffected sibling was heterozygous for one of the variants. Functional assays and mouse model also supported the association.Created: 3 Jan 2017, 10:07 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia
Publications
Gene: xrcc1 has been classified as Green List (High Evidence).
Tag founder-effect tag was added to gene: XRCC1.
Publications for gene: XRCC1 were set to 28002403
Phenotypes for gene: XRCC1 were changed from ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia to Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633
XRCC1 was added to Hereditary ataxiapanel. Sources: Literature
XRCC1 was created by ellenmcdonagh