Hereditary ataxia with onset in adulthood
Gene: XRCC1The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 9 Mar 2022, 5:26 p.m. | Last Modified: 9 Mar 2022, 5:26 p.m.
Panel Version: 2.144
Comment on list classification: This gene will be flagged for GMS review to determine whether there is enough evidence to include XRCC1 on this panel as Green. Only one case with adult onset and the other two with onset in childhood, however inclusion may be justified to ensure identification of edge cases.
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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, 3:42 p.m. | Last Modified: 28 Jun 2021, 3:42 p.m.
Panel Version: 2.80
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633
Publications
Single East Indian family. Not on Ox or Shef. Mismatch repair gene.Created: 27 Apr 2019, 7:39 p.m.
Added watchlist tag. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene AmberCreated: 1 Aug 2019, 3:43 p.m. | Last Modified: 1 Aug 2019, 3:43 p.m.
Panel Version: 1.188
Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group
Created: 27 Apr 2019, 8:55 p.m.
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.Created: 15 Apr 2019, 10:21 a.m.
Only a single individual reported, compound het for LoF variants. VERY strong functional evidence.Created: 15 Apr 2019, 10:06 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Autosomal recessive spinocerebellar ataxia 26, 617633
Tag Q2_21_expert_review was removed from gene: XRCC1.
Tag Q2_21_expert_review tag was added to gene: XRCC1.
Gene: xrcc1 has been classified as Amber List (Moderate Evidence).
Tag watchlist was removed from gene: XRCC1. 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; Autosomal recessive spinocerebellar ataxia 26, 617633 to Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633
Tag watchlist tag was added to gene: XRCC1.
Gene: xrcc1 has been classified as Amber List (Moderate Evidence).
Source London North GMS was added to XRCC1.
Added phenotypes Autosomal recessive spinocerebellar ataxia 26, 617633 for gene: XRCC1
Source NHS GMS was added to XRCC1.
Source Wessex and West Midlands GLH was added to XRCC1.
Louise Daugherty: Comment on phenotypes: Implica
gene: XRCC1 was added gene: XRCC1 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,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