Three novel mutations responsible for Cockayne syndrome group A.
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.
Ren
Yan
Y
Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
Saijo
Masafumi
M
Nakatsu
Yoshimichi
Y
Nakai
Hiroshi
H
Yamaizumi
Masaru
M
Tanaka
Kiyoji
K
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
C095472:ERCC8 protein, human; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D045643:DNA Repair Enzymes