Hereditary ataxia with onset in adulthood

Gene: ERCC4

The 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

Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least nine variants reported in at least seven cases of Xeroderma pigmentosum, group F OMIM:278760, where neurodegeneration and ataxia was present (PMID 29403087; 28431612; 29892709).

Created: 20 May 2021, 11:40 a.m. | Last Modified: 20 May 2021, 11:40 a.m.

Panel Version: 2.57

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 20 May 2021, 11:31 a.m. | Last Modified: 20 May 2021, 11:31 a.m.

Panel Version: 2.56

Green List (high evidence)

Bi-allelic variants in ERCC4 cause a range of phenotypes, including xeroderma pigmentosum complementation group F (XP-F), Cockayne syndrome, and Fanconi anaemia. Seven unrelated individuals reported with slowly progressive cerebellar ataxia and cognitive decline with choreiform involuntary movement, with onset in adolescence/adulthood. Brain MRIs demonstrated atrophy that included the cerebellum and brainstem. Of note, cutaneous symptoms were very mild in 5/7: there was normal to very mild pigmentation of exposed skin areas and/or an equivocal history of pathological sunburn.
Sources: Expert list

Created: 13 Sep 2020, 11:32 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebellar ataxia; Xeroderma pigmentosum, group F, MIM# 278760

Publications

• 29403087
• 28431612
• 29892709

Variants in this GENE are reported as part of current diagnostic practice