title: Identification of two missense mutations of ERCC6 in three Chinese sisters with Cockayne syndrome by whole exome sequencing.
abstract: 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.
authors.affiliation: BGI-shenzhen, Shenzhen, 518083, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Prenatal Diagnosis Center, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, 518048, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Chen
authors.affiliation: BGI-shenzhen, Shenzhen, 518083, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ye
authors.affiliation: BGI-shenzhen, Shenzhen, 518083, China.
authors.forename: Lingna
authors.initials: L
authors.lastname: Fei
authors.affiliation: BGI-shenzhen, Shenzhen, 518083, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: BGI-shenzhen, Shenzhen, 518083, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Prenatal Diagnosis Center, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, 518048, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Geng
authors.affiliation: BGI-shenzhen, Shenzhen, 518083, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yi
authors.affiliation: Prenatal Diagnosis Center, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, 518048, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Xie
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D003057:Cockayne Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*; D017124:Conserved Sequence; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D000075223:Poly-ADP-Ribose Binding Proteins; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D035781:Siblings; D014057:Tomography, X-Ray Computed
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes