title: Three novel mutations responsible for Cockayne syndrome group A.
abstract: 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.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.forename: Masafumi
authors.initials: M
authors.lastname: Saijo
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Nakatsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakai
authors.forename: Masaru
authors.initials: M
authors.lastname: Yamaizumi
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D019943:Amino Acid Substitution; D015139:Blotting, Southern; D003057:Cockayne Syndrome / Q000235:genetics*; D045643:DNA Repair Enzymes; D006801:Humans; D009154:Mutation; D017354:Point Mutation; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014157:Transcription Factors
chemical_list: C095472:ERCC8 protein, human; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D045643:DNA Repair Enzymes