title: Molecular epidemiology and functional assessment of novel allelic variants of SLC26A4 in non-syndromic hearing loss patients with enlarged vestibular aqueduct in China.
abstract: BACKGROUND
  Mutations in SLC26A4, which encodes pendrin, are a common cause of deafness. SLC26A4 mutations are responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA). The mutation spectrum of SLC26A4 varies widely among ethnic groups. To investigate the incidence of EVA in Chinese population and to provide appropriate genetic testing and counseling to patients with SLC26A4 variants, we conducted a large-scale molecular epidemiological survey of SLC26A4.
  
  
  METHODS
  A total of 2352 unrelated non-syndromic hearing loss patients from 27 different regions of China were included. Hot spot regions of SLC26A4, exons 8, 10 and 19 were sequenced. For patients with one allelic variant in the hot spot regions, the other exons were sequenced one by one until two mutant alleles had been identified. Patients with SLC26A4 variants were then examined by temporal bone computed tomography scan for radiological diagnosis of EVA. Ten SLC26A4 variants were cloned for functional study. Confocal microscopy and radioisotope techniques were used to examine the membrane expression of pendrin and transporter function.
  
  
  RESULTS
  Of the 86 types of variants found, 47 have never been reported. The ratio of EVA in the Chinese deaf population was at least 11%, and that in patients of Han ethnicity reached at least 13%. The mutational spectrum and mutation detection rate of SLC26A4 are distinct among both ethnicities and regions of Mainland China. Most of the variants caused retention of pendrin in the intracellular region. All the mutant pendrins showed significantly reduced transport capability.
  
  
  CONCLUSIONS
  An overall description of the molecular epidemiological findings of SLC26A4 in China is provided. The functional assessment procedure can be applied to identification of pathogenicity of variants. These findings are valuable for genetic diagnosis, genetic counseling, prenatal testing and pre-implantation diagnosis in EVA families.
authors.affiliation: Department of Otolaryngology, Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Yuan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Guo
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Guozheng
authors.initials: G
authors.lastname: Zhang
authors.forename: Guojian
authors.initials: G
authors.lastname: Wang
authors.forename: Mingyu
authors.initials: M
authors.lastname: Han
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.forename: Shiming
authors.initials: S
authors.lastname: Yang
authors.forename: David Z Z
authors.initials: DZ
authors.lastname: He
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002681:China; D005260:Female; D014644:Genetic Variation; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D011859:Radiography; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters