title: Sensorineural hearing loss caused by mutations in two alleles of both GJB2 and SLC26A4 genes.
abstract: BACKGROUND
  Most studies of the molecular etiology of sensorineural hearing loss have described deafness as a monogenic disease encompassing double-allele mutations for patients with autosomal recessive deafness. Here, we report the first case of autosomal recessive genetic deafness in an enlarged vestibular aqueduct syndrome (EVAS) patient with biallelic mutations in two deafness genes.
  
  
  METHODS
  Temporal computed tomography (CT), complete physical and otoscopic examinations, and an audiological study, including tympanometry, pure-tone audiometry or auditory steady-state response (ASSR), were carried out. Exon 2 of GJB2 and the coding exons of SLC26A4 were sequenced.
  
  
  RESULTS
  A patient with an enlarged vestibular aqueduct was found to carry c.1229C>T/c.1079C>T compound heterozygous mutations in SLC26A4.This individual also carried c.257C>G/c.299-300delAT compound heterozygous mutations in GJB2. As a result, the recurrent risk of the patient's siblings increased significantly from 25% for typical autosomal recessive deafness to 43.75%.
  
  
  CONCLUSIONS
  The findings of the present study challenge the traditional diagnostic strategy in which testing is generally considered complete upon identification of a double-allele mutation within one gene, with significant implications for genetic counseling and risk prediction. Our results suggest that, with advances in sequencing technology, it will be possible and necessary to test all known deafness genes in the near future, as this will likely allow more accurate genetic counseling of patients.
authors.affiliation: Department of Otolaryngology, PLA General Hospital, Beijing, PR China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Huang
authors.forename: Dongyi
authors.initials: D
authors.lastname: Han
authors.forename: Guojian
authors.initials: G
authors.lastname: Wang
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yueshuai
authors.initials: Y
authors.lastname: Song
authors.forename: Mingyu
authors.initials: M
authors.lastname: Han
authors.forename: Zhengyi
authors.initials: Z
authors.lastname: Chen
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
mesh_terms: D000483:Alleles; D002648:Child; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000002:abnormalities
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26