title: Two Novel Heterozygous Mutations in ERCC8 Cause Cockayne Syndrome in a Chinese Patient.
abstract: BACKGROUND
  Cockayne syndrome (MIM #133540, Cockayne syndrome B; 216400, Cockayne syndrome A) is a rare autosomal recessive inherited disease in which the characteristic symptoms are premature aging, cachectic dwarfism, lack of subcutaneous fat, neurological alterations, light sensitivity, and failure to thrive. The mutated gene responsible for this syndrome has been identified as usually either CSA (CKN1, ERCC8) or CSB (ERCC6). In this study, we describe the case of a 7-year-old Chinese boy with characteristic symptoms of Cockayne syndrome A and the conduction of mutation screening of the CSA gene.
  
  
  METHODS
  The patient was diagnosed with Cockayne syndrome in the pediatrics clinic for growth failure and developmental delay. We collected peripheral blood samples of the patient and his parents and then extracted the genomic DNA. DNA samples from control subjects and the patient were subjected to polymerase chain reaction amplification. All exons and the flanking intron-exon boundaries of CSA were amplified; then, the polymerase chain reaction products were directly sequenced for mutation screening.
  
  
  RESULTS
  Two novel heterozygous CSA mutations, c.551-2A>C and c.394_398delTTACA, were identified in the patient. The c.551-2A>C mutation originates from his father and changed the splice acceptor site AG to CG, thus possibly causing alternative splicing. The c.394_398delTTACA from his mother caused a frameshift after the amino acid at position 132, thus introducing a premature stop codon in the gene sequence.
  
  
  CONCLUSIONS
  These mutations extend the mutation spectrum of Cockayne syndrome in the context of Chinese race and provide possibilities of prenatal diagnosis for future offsprings in this family.
authors.affiliation: Department of Pediatrics, Peking University Third Hospital, Beijing, China.
authors.forename: Yun-Pu
authors.initials: YP
authors.lastname: Cui
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China; Human Disease Genomics Center, Peking University, Beijing, China.
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Peking University Third Hospital, Beijing, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Peking University Third Hospital, Beijing, China. Electronic address: Xinli_Wang1217@yahoo.com.cn.
authors.forename: Xin-Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Human Disease Genomics Center, Peking University, Beijing, China; Department of Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Nan
authors.affiliation: Human Disease Genomics Center, Peking University, Beijing, China; Department of Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China. Electronic address: hongshan@bjmu.edu.cn.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Zhao
mesh_terms: D044466:Asian People / Q000235:genetics; D002648:Child; D002681:China; D003057:Cockayne Syndrome / Q000235:genetics*; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C095472:ERCC8 protein, human; D014157:Transcription Factors; D045643:DNA Repair Enzymes
keywords: CSA; Cockayne syndrome; autosomal recessive; mutation