Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome
Gene: ERCC8Comment on mode of pathogenicity: See reviewer comments. Loss-of-function variants indicated as the mutation consequence in Gene2Phenotype.Created: 25 Jul 2016, 9:46 a.m.
Comment on list classification: Promoted from red to green due to two expert reviews. It is a confirmed DD gene for Cockayne Syndrome Type A.Created: 25 Jul 2016, 9:45 a.m.
Relevant phenotype and mode of inheritance sourced from OMIM.Created: 8 Jan 2016, 12:12 p.m.
The Northern Genetics Service offer Sanger sequencing for all 12 exons of ERCC8 (NM000082.3), as an NHS service and as part of the Cockayne syndrome Natural History study, which comprises the largest cohort of patients with CS reported to date.Created: 12 Feb 2016, 1:35 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cockayne syndrome phenotype and UV-sensitive syndrome
Publications
Mode of pathogenicity
Other
Variants in this GENE are reported as part of current diagnostic practice
Mutations in ERCC8 (CSA) account for 25-30% of genetically confirmed cases of Cockayne syndrome (CS; PMID: 26204423). There are regional variations, with a greater proportion of ERCC8 mutations accounting for the phenotype in Japan and parts of the Middle East. Missense mutations in ERCC8 may result in a UV-sensitive syndrome phenotype, i.e. patients exhibit only dermal photosensitivity (with no increased skin cancer risk) and hyperpigmentation in sun exposed areas, and do not have small stature, microcephaly, developmental delay or the premature pathological ageing that characterises the CS phenotype. As our experience increases, a putative relationship between mutation type and position, and phenotype is emerging.
The Northern Genetics Service Molecular Genetics Laboratory (Newcastle upon Tyne NHS Hospitals FT) provides diagnostic sequencing independently and as part of the Cockayne syndrome Natural History study, and I believe has the greatest experience with mutation positive cases for ERCC6 and ERCC8 internationally.Created: 10 Feb 2016, 9:56 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
I have already supplied the HPO terms for CS to Genomics England, based on our recent study findings (PMID: 26204423) - all of these are applicable to the phenotypes associated with both ERCC6 and ERCC8 - I am happy to annotate this review with them if necessary; a UV-sensitive syndrome phenotype may also occur.
Publications
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cockayne syndrome A; UV-sensitive syndrome 2
28/Nov/2016: Panel combined and revised due to external and internal review.
This gene has been classified as Green List (High Evidence).
Phenotypes for ERCC8 were set to Cockayne syndrome, type A; Cockayne syndrome phenotype and UV-sensitive syndrome; PMID: 26204423
Publications for ERCC8 were set to 26204423
Mode of pathogenicity for ERCC8 was changed to Other - please provide details in the comments
ERCC8 was added to Cockayne and Xeroderma Pigmentosum-like disorderspanel. Source: Eligibility statement prior genetic testing ERCC8 was added to Cockayne and Xeroderma Pigmentosum-like disorderspanel. Source: Other ERCC8 was added to Cockayne and Xeroderma Pigmentosum-like disorderspanel. Source: Expert Review Green ERCC8 was added to Cockayne and Xeroderma Pigmentosum-like disorderspanel. Source: Radboud University Medical Center, Nijmegen ERCC8 was added to Cockayne and Xeroderma Pigmentosum-like disorderspanel. Source: Illumina TruGenome Clinical Sequencing Services Model of inheritance for gene ERCC8 was set to BIALLELIC, autosomal or pseudoautosomal
ERCC8 was created by ellenmcdonagh
ERCC8 was added to Cockayne and Xeroderma Pigmentosum-like disorderspanel. Sources: UKGTN