title: R75Q de novo dominant mutation of GJB2 in a Chinese family with hearing loss and palmoplantar keratoderma.
abstract: OBJECTIVE
  Mutations in the GJB2 gene encoding connexin 26 (Cx26) are major causes of hereditary deafness. This study aimed to characterize the mutation profiles of the GJB2 gene in a Chinese family with sensorineural hearing loss.
  
  
  METHODS
  A Chinese family that included three individuals with sensorineural hearing loss and palmoplantar keratoderma underwent complete physical examinations, audiological examinations including pure tone audiometry and auditory brainstem response, skin pathological examination, and temporal CT scans. The entire coding region of GJB2, GJB3, GJB6, and the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN) were sequenced. Structural analysis was performed to detect the effects of mutation on the tertiary structure of Cx26.
  
  
  RESULTS
  A dominant GJB2 mutation, c.224G>A (p.Arg75Gln, p.R75Q), was detected in the family. No other mutation was identified in GJB2, GJB3, GJB6, or the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN). Structural analysis revealed that the p.R75Q mutation likely affects the structural stability and permeation properties of the Cx26 gap junction channel.
  
  
  CONCLUSIONS
  Our findings provide further evidence of a correlation between the p.R75Q mutation in Cx26 and a syndromic hearing impairment with palmoplantar keratoderma.
authors: Clinical Genetics Department, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China.
authors: Shu-juan
authors: SJ
authors: Jiang
authors: Dermatological Department, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China.
authors: Zheng-hong
authors: ZH
authors: Di
authors: Clinical Genetics Department, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China.
authors: Dan
authors: D
authors: Huang
authors: Orthopedics Department, The First Affiliated Hospital, China Medical University, 110001 Shenyang, Liaoning, PR China.
authors: Jiu-bin
authors: JB
authors: Zhang
authors: Clinical Genetics Department, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China.
authors: Yuan-yuan
authors: YY
authors: Zhang
authors: Virus Laboratory, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China.
authors: Shu-qin
authors: SQ
authors: Li
authors: Clinical Genetics Department, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China. Electronic address: her@sj-hospital.org.
authors: Rong
authors: R
authors: He
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002681:China; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics*; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: China; De novo mutation; GJB2 gene; Hearing impairment; Palmoplantar keratoderma; Structural analysis