Three novel mutations responsible for Cockayne syndrome group A

Genes Genet Syst. 2003 Feb;78(1):93-102. doi: 10.1266/ggs.78.93.


Cockayne syndrome (CS) is a rare autosomal recessive disease, which shows diverse clinical symptoms such as photosensitivity, severe mental retardation and developmental defects. CS cells are hypersensitive to killing by UV-irradiation and defective in transcription-coupled repair. Two genetic complementation groups in CS (CS-A and CS-B) have been identified. We analyzed mutations of the CSA gene in 5 CS-A patients and identified 3 types of mutations. Four unrelated CS-A patients (CS2OS, CS2AW, Nps2 and CS2SE) had a deletion including exon 4, suggesting that there is a founder effect on the CSA mutation in Japanese CS-A patients. Patient CS2SE was a compound heterozygote for this deletion and an amino acid substitution at the 106th glutamine to proline (Q106P) in the WD-40 repeat motif of the CSA protein, which resulted in a defective nucleotide excision repair. Patient Mps1 had a large deletion in the upstream region including exon 1 of the CSA gene. Our results indicate that a rapid and reliable diagnosis of CSA mutations could be achieved in CS-A patients by PCR or PCR-RFLP and that the Q106P mutation could alter the propeller structure of the CSA protein which is important for the formation of the CSA protein complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Blotting, Southern
  • Cockayne Syndrome / genetics*
  • DNA Repair Enzymes
  • Humans
  • Mutation*
  • Point Mutation
  • Proteins / genetics*
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion
  • Transcription Factors


  • ERCC8 protein, human
  • Proteins
  • RNA, Messenger
  • Transcription Factors
  • DNA Repair Enzymes