ERCC8 and Cockayne syndrome type 2

ERCC8 encodes the CSA protein, a key component of transcription-coupled nucleotide excision repair. Biallelic ERCC8 mutations underlie Cockayne syndrome type A, an autosomal recessive progeroid disorder marked by growth failure, microcephaly, and photosensitivity, but no definitive ERCC8‐related Cockayne syndrome type 2 cases have been documented. Cockayne syndrome type 2 is classically caused by ERCC6 (CSB) defects, presenting with severe neurological decline and systemic premature aging. Although ERCC8 loss-of-function alleles (e.g., c.394_398del (p.Leu132AsnfsTer6)) recur in Chinese CS-A cohorts, none segregate with a MONDO_0019570 phenotype (PMID:29057985). Functional assays confirm ERCC8 deficiency impairs CSA-mediated repair in CS-A fibroblasts but do not support a role in CS type 2 (PMID:15744458). In the absence of ERCC8 variants in bona fide CS type 2 families, the gene–disease link is disputed. Key Take-home: ERCC8 testing is validated for Cockayne syndrome type A but not for Cockayne syndrome type 2.

References

• Scientific reports • 2017 • Molecular spectrum of excision repair cross-complementation group 8 gene defects in Chinese patients with Cockayne syndrome type A. PMID:29057985
• Journal of human genetics • 2005 • Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects. PMID:15744458

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