title: De novo dominant mutation of GJB2 in two Chinese families with nonsyndromic hearing loss.
abstract: BACKGROUND
  Mutations in the GJB2 gene are the most common cause of nonsyndromic autosomal recessive sensorineural hearing loss. A few mutations in GJB2 have also been reported to cause dominant nonsyndromic or syndromic hearing loss. However, de novo or dominant mutation in GJB2 is not common in Chinese populations.
  
  
  METHODS
  Two probands with hearing impairment from unrelated Chinese families are reported here. Temporal CT scan, complete physical (including skin and hair) and otoscopic examinations, and an audiological study, including tympanometry, auditory brainstem response (ABR), auditory steady-state response (ASSR), and 40Hz-auditory event-related potential (40 Hz-AERP), were carried out. The two exons of GJB2, the coding exons of SLC26A4, and mitochondrial 12S rRNA were sequenced.
  
  
  RESULTS
  Sequencing of GJB2 in the two cases showed a heterozygous c.551G>A(p.R184Q) mutation, which was not found in other family members. Additionally, no other mutation in GJB2 was identified in the two family members. Paternity was confirmed by genotype analysis of 15 informative short tandem repeats (STRs) from the chromosomes. Sequence analysis of the coding exons of SLC26A4 and mitochondrial 12S rRNA was performed but no sequence aberration or deletion was found.
  
  
  CONCLUSIONS
  A de novo GJB2 p.R184Q mutation can cause severe-to-profound bilateral sensorineural hearing impairment. Although not common in Chinese patients with hearing loss, it is important to identify the specific phenotype and genotype correlations of the de novo dominant mutation in GJB2.
authors.affiliation: Department of Otolaryngology, PLA General Hospital, Do.28 Fuxing Rode, Beijing 100853, People's Republic of China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Huang
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Dongyi
authors.initials: D
authors.lastname: Han
authors.forename: Dongyang
authors.initials: D
authors.lastname: Kang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yan
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
mesh_terms: D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D006320:Hearing Tests; D006801:Humans; D007223:Infant; D009154:Mutation / Q000235:genetics*; D010375:Pedigree
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26