title: Molecular etiology of hearing impairment associated with nonsyndromic enlarged vestibular aqueduct in East China.
abstract: Recessive mutations in SLC26A4 and in rarer cases double heterozygous mutations of FOXI1/SLC26A4 and KCNJ10/SLC26A4 lead to hearing impairment associated with enlarged vestibular aqueduct (EVA), the most common inner ear malformation. In our large cohort study, we addressed several important questions to the molecular etiology of this disorder. The overall prevalence of SLC26A4 mutations in nonsyndromic childhood sensorineural hearing loss (11.2%, 37/330) were determined by sequencing of SLC26A4 in 330 hearing impaired children who did not undergo inner ear radiologic imaging prior to their genetic test. The penetrance of EVA in bi-allelic SLC26A4 mutation carriers (100%, 37/37) was determined by follow-up computed tomography scanning. Combined with the study of 140 additional probands diagnosed with nonsyndromic EVA, we characterized the mutation spectrum of SLC26A4 in East China, which consisted of 19 novel SLC26A4 mutations and differed from those reported in other regions of China.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yongchuan
authors.initials: Y
authors.lastname: Chai
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Huang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tao
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D002681:China; D017124:Conserved Sequence; D051858:Forkhead Transcription Factors / Q000235:genetics; D034381:Hearing Loss / Q000175:diagnosis / Q000209:etiology*; D006319:Hearing Loss, Sensorineural / Q000150:complications* / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D016415:Sequence Alignment; D012720:Severity of Illness Index; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000002:abnormalities*; D000098854:Kcnj10 Channel
chemical_list: C477894:FOXI1 protein, human; D051858:Forkhead Transcription Factors; D000098854:Kcnj10 Channel; D026901:Membrane Transport Proteins; D024661:Potassium Channels, Inwardly Rectifying; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters
keywords: SLC26A4; enlargement of vestibular aqueduct; hearing impairment; mutation