Clinical and molecular characteristics of ERCC8-related Cockayne syndrome in three Chinese patients: case report and literature review

Cockayne syndrome (CS) is a rare autosomal recessive disorder primarily caused by biallelic variants in ERCC8 gene (CSA). Phenotype heterogeneity complicates clinical diagnosis, Trio-based sequencing improves diagnosis and genetic counseling for CS patient. We report three CS children from our center. ERCC8 gene variants identified by Trio-based Whole-Exome Sequencing (Trio-WES) and validated by Sanger sequencing and quantitative PCR (qPCR). A literature review of ERCC8 variants in Chinese CS patients was conducted to assess genotype and clinical features. All three patients demonstrated core CS features (microcephaly, growth delay/failure to thrive, developmental delay) with variable additional findings and ERCC8 variants: c.400-2delA and c.371_372delTG (p.L124Qfs*15) compound heterozygous variants in patient 1, and homozygous exon 4 deletion and exons 6–11 deletion in patient 2 and patient 3, respectively. In silico analyses suggested disruption of WD40 domains and loss of functional regions. The Chinese patients (52 patients from 18 studies plus our three cases) were analyzed with ERCC8 variant genotype and CS phenotype features. Trio-WES with comprehensive phenotyping enables molecular diagnosis in CS. The findings support targeted ERCC8 testing in suspected CS, and emphasize genotype and phenotype value for counseling and management.