Two novel mutations in ERCC6 cause Cockayne syndrome B in a Chinese family

Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized principally by progressive growth failure, neurologic abnormality and premature aging. Mutations of excision repair cross-complementation group 6 (ERCC6) and ERCC8 are predominantly responsible for CS, of which mutation of ERCC6 accounts for approximately two thirds of cases. The current report describes two siblings with severe neurologic abnormality and premature aging. Whole exome sequencing identified two novel mutations in ERCC6 that had not been previously reported. One was a nonsense mutation at codon 612 in exon 9 (c.1834C>T, p.Arg612Ter), and the other a missense mutation at codon 975 in exon 16 (c.2923C>T, p.Arg975Trp). Cosegregation analysis revealed c.1834C>T was paternal and c.2923C>T was maternal. A healthy baby with no mutated alleles was delivered based on prenatal diagnosis performed by genetic testing of amniocytes for the causative mutation. The present study will enrich the clinical and genetic spectrum of CS in China and world wide, and provides more evidence for future genotype-phenotype studies.