Identification of two missense mutations of ERCC6 in three Chinese sisters with Cockayne syndrome by whole exome sequencing

PLoS One. 2014 Dec 2;9(12):e113914. doi: 10.1371/journal.pone.0113914. eCollection 2014.


Cockayne syndrome (CS) is a rare autosomal recessive disorder, the primary manifestations of which are poor growth and neurologic abnormality. Mutations of the ERCC6 and ERCC8 genes are the predominant cause of Cockayne syndrome, and the ERCC6 gene mutation is present in approximately 65% of cases. The present report describes a case of Cockayne syndrome in a Chinese family, with the patients carrying two missense mutations (c.1595A>G, p.Asp532Gly and c.1607T>G, p.Leu536Trp) in the ERCC6 gene in an apparently compound heterozygote status, especially, p.Asp532Gly has never been reported. The compound heterozygote mutation was found in three patients in the family using whole exome sequencing. The patients' father and mother carried a heterozygous allele at different locations of the ERCC6 gene, which was confirmed by Sanger DNA sequencing. The two mutations are both located in the highly conserved motif I of ATP-binding helicase and are considered "Damaging," "Probably Damaging," "Disease Causing," and "Conserved", indicating the role of DNA damage in the pathogenetic process of the disease. The results not only enrich the ERCC6 mutations database, but also indicate that whole exome sequencing will be a powerful tool for discovering the disease causing mutations in clinical diagnosis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Asian People / genetics*
  • Base Sequence
  • Cockayne Syndrome / diagnostic imaging
  • Cockayne Syndrome / genetics*
  • Conserved Sequence
  • DNA Helicases / chemistry
  • DNA Helicases / genetics*
  • DNA Mutational Analysis
  • DNA Repair Enzymes / chemistry
  • DNA Repair Enzymes / genetics*
  • Exome / genetics*
  • Exons / genetics
  • Female
  • Heterozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Molecular Sequence Data
  • Mutation / genetics
  • Mutation, Missense / genetics*
  • Pedigree
  • Poly-ADP-Ribose Binding Proteins
  • Protein Structure, Tertiary
  • Reproducibility of Results
  • Siblings*
  • Tomography, X-Ray Computed


  • Poly-ADP-Ribose Binding Proteins
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes

Grants and funding

This work was supported by the Science and Technology Project of Shenzhen (201001016). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.