Ataxia and cerebellar anomalies - narrow panel
Gene: XRCC1
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.
Panel Version: 3.30
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 to Green at the next GMS panel update (see details below).
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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 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, 3:32 p.m. | Last Modified: 28 Jun 2021, 3:36 p.m.
Panel Version: 2.214
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633
Publications
Three South Asian cases (one with early adult onset and the other two with onset in childhood) reported with slowly progressive cerebellar ataxia accompanied by sensorimotor neuropathy. All with the recurrent splice variant (c.1293G>C, 2 homozygotes and a compound heterozygote). Mice with conditional deletion of the Xrcc1 gene in the brain showed cerebellar ataxia.Created: 13 Sep 2020, 8:02 a.m. | Last Modified: 13 Sep 2020, 8:02 a.m.
Panel Version: 2.12
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spinocerebellar ataxia, autosomal recessive 26 MIM#617633
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_21_rating was removed from gene: XRCC1.
Source Expert Review Green was added to XRCC1. Source NHS GMS was added to XRCC1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag founder-effect tag was added to gene: XRCC1. Tag Q2_21_rating tag was added to gene: XRCC1.
Gene: xrcc1 has been classified as Amber List (Moderate Evidence).
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
Rebecca Foulger: Comment on list classification
gene: XRCC1 was added gene: XRCC1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red Mode of inheritance for gene: XRCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: XRCC1 were set to 28002403 Phenotypes for gene: XRCC1 were set to ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia