title: Hearing loss associated with an unusual mutation combination in the gap junction beta 2 (GJB2) gene in a Chinese family.
abstract: OBJECTIVE
  To assess the molecular etiology of nonsyndromic sensorineural hearing loss (NSHL) in members of an affected Chinese family.
  
  
  METHODS
  Common hearing-related genes including gap junction beta 2 (GJB2), SLC26A4, mitochondrial DNA 12S rRNA, GJB3 and GJB6 were examined in a family consisting of a normal hearing father, an NSHL-affected mother, one normal-hearing child and three NSHL-affected children. Specific primers were used in polymerase chain reactions to amplify the coding regions of the above genes from the peripheral blood DNA from each family member, and the genes were analyzed by direct sequencing. The subjects were evaluated for phenotypic characterization using audiometric testing and radiological examination of the inner ear.
  
  
  RESULTS
  Pathogenic mutations in the GJB2 gene were identified. The affected mother showed a heterozygous G→A transition at nucleotide 232, resulting in an alanine to threonine substitution at codon 78 (p.A78T), and the normal hearing father had a c.35insG insertion mutation. The three affected children displayed heterozygosity for the GJB2 mutations, showing a previously unreported combination of c.35insG and c.232G>A.
  
  
  CONCLUSIONS
  The GJB2 mutations account for a significant proportion of NSHL in affected individuals worldwide. Genetic and audiological data analysis of a Chinese family with NSHL revealed a novel c.35insG/c.232G>A compound heterozygous state. Our results highlight the complexity of the GJB2 genotypes and phenotypes.
authors: Department of Otolaryngology, Head & Neck Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050018, Hebei, China; Department of Otolaryngology, Head & Neck Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors: Aiping
authors: A
authors: Huang
authors: Department of Otolaryngology, Head & Neck Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors: Yongyi
authors: Y
authors: Yuan
authors: Department of Otolaryngology, Head & Neck Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050018, Hebei, China.
authors: Naichao
authors: N
authors: Duan
authors: Department of Otolaryngology, Head & Neck Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050018, Hebei, China.
authors: Xinxia
authors: X
authors: Jiang
authors: Department of Otolaryngology, Head & Neck Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050018, Hebei, China.
authors: Baoshan
authors: B
authors: Wang
authors: Department of Otolaryngology, Head & Neck Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050018, Hebei, China.
authors: Yanping
authors: Y
authors: Liu
authors: Department of Otolaryngology, Head & Neck Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors: Dongyang
authors: D
authors: Kang
authors: Department of Otolaryngology, Head & Neck Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors: Xin
authors: X
authors: Zhang
authors: Department of Otolaryngology, Head & Neck Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050018, Hebei, China. Electronic address: zqw301@163.com.
authors: Qingwen
authors: Q
authors: Zhu
authors: Department of Otolaryngology, Head & Neck Surgery, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: daipu301@vip.sina.com.
authors: Pu
authors: P
authors: Dai
mesh_terms: D000328:Adult; D002681:China; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: GJB2 mutation; Hearing loss; Phenotype