title: [Mutation screening for the causative gene in a four-generation Chinese pedigree with progressive cardiac conduction defect].
abstract: OBJECTIVE
  To define the potential causative gene mutation in a Chinese pedigree with progressive cardiac conduction defect (PCCD).
  
  
  METHODS
  Sanger sequencing was performed to define potential causative gene mutation in a four-generation family with 68 members including seven PCCD patients (5 male) from 2010 to 2015.No causative gene was detected by screening known candidate genes related to PCCD including SCN5A, NKX2.5 and LMNA.High-throughput sequencing technology on exon-enriched DNA was then used to search the causative genes in 2 patients and one normal family member.
  
  
  RESULTS
  Eight new non-synonymous single nucleotide variants including AQP7 gene (exon5: c.T343C: p.Y115H), CACNA1B gene (NM_001243812: exon19: c.A2986G: p.T996A), CATSPERB gene (exon27: c.C3254G: p.P1085R), CLCA2 gene (exon11: c.G1725T: p.W575C), CLCA3P gene (ncRNA_intronic), MYLK-AS1 gene (ncRNA_intronic), TTN gene (ncRNA_UTR3), LMNA gene (LMNA: NM_170708: exon5: c.C922T: p.Q308X) were identified by comparing and filtering the results with known public databases.Then, more detailed biological analysis on these 8 genes was conducted.Traditional Sanger sequencing validated the exome sequencing results, and found that the mutation c. 1725G﹥T in gene CLCA2 segregated with the phenotype of this PCCD pedigree.The mutation c. 1725G﹥T in gene CLCA2 was thus be considered as the causative PCCD gene in this pedigree from the perspective of genetics and genomics.
  
  
  CONCLUSIONS
  The heterozygote mutation c. 1725G﹥T in gene CLCA2 might be causative gene in this PCCD pedigree.This finding adds new gene mutation variant responsible for PCCD.
authors.affiliation: Reproductive and Genetic Center of Central Hospital of Xiangtan, Xiangtan 411100, China.
authors.forename: X J
authors.initials: XJ
authors.lastname: Tan
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.forename: F
authors.initials: F
authors.lastname: He
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: Y S
authors.initials: YS
authors.lastname: Jiang
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: X H
authors.initials: XH
authors.lastname: Huang
authors.forename: Z S
authors.initials: ZS
authors.lastname: Sun
authors.forename: Z H
authors.initials: ZH
authors.lastname: Li
mesh_terms: D044466:Asian People; D000075224:Cardiac Conduction System Disease; D002681:China; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006327:Heart Block / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: C120066:CLCA2 protein, human; D018118:Chloride Channels