title: [Molecular genetic study of a family featuring cardiac conduction block].
abstract: OBJECTIVE To explore the genetic mechanism for a family affected with cardiac conduction block. METHODS Affected family members were screened for potential mutations of known candidate genes. As no pathogenic mutation was found, two patients and one healthy member from the family were further analyzed by exomic sequencing followed by Sanger sequencing. The pathogenicity of suspected mutation was analyzed using bioinformatics software. RESULTS Sequencing of the full exome has identified a c.G1725T mutation in the CLCA2 gene. Sanger sequencing has detected the same mutation in all five patients, but not in the normal member from the family. Bioinformatics analysis indicated that the mutation has resulted in substitution of the 575th amino acid cysteine (C) by tryptophan (W). The site is highly conserved and becomes pathogenic with the mutation. CONCLUSION The heterozygous c.G1725T mutation in exon 11 of the CLCA2 gene probably underlies the disease and fit the autosomal dominant pattern of inheritance.
authors.affiliation: Reproductive and Genetic Center of Central Hospital of Xiangtan, Xiangtan, Hunan 411100, P.R. China. Email: changdaot@163.com.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tan
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Yongjuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Xianghong
authors.initials: X
authors.lastname: Huang
authors.forename: Zhishan
authors.initials: Z
authors.lastname: Sun
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D018118:Chloride Channels / Q000235:genetics*; D019295:Computational Biology; D005260:Female; D006327:Heart Block / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: C120066:CLCA2 protein, human; D018118:Chloride Channels