title: Mono-allelic mutations of SLC26A4 is over-presented in deaf patients with non-syndromic enlarged vestibular aqueduct.
abstract: OBJECTIVE
  Recessive mutations of SLC26A4 are the major cause of hearing impairment associated with enlarged vestibular aqueduct (EVA). In a significant percentage of non-syndromic EVA patients, however, only mono-allelic mutations of SLC26A4 can be identified. In this study, we aimed to evaluate whether presence of mono-allelic mutations of SLC26A4 in those patients was coincidental or etiologically associated with the disorder.
  
  
  METHODS
  The exons and flanking splicing sites of SLC26A4 were sequenced in 150 Chinese Han deaf probands with non-syndromic EVA. c.919-2A >G and p.H723R, two frequent mutations of SLC26A4 in Chinese Hans, were screened by an allele-specific PCR-based array in 3056 ethnically-matched normal hearing controls. The frequency of mono-allelic c.919-2A >G and p.H723R mutations was determined in each group. The statistical significance of the difference was analyzed by Fisher's exact test.
  
  
  RESULTS
  Bi-allelic, mono-allelic and no mutation of SLC26A4 were detected in 98 (65.3%), 18 (12%) and 34 (22.67%) deaf probands with non-syndromic EVA, respectively. The frequency of mono-allelic c.919-2A >G and p.H723R mutations were significantly higher in the 150 deaf probands with non-syndromic EVA (8.67%) than in the 3056 normal hearing controls (1.4%, P=1.8×10(-6)).
  
  
  CONCLUSIONS
  Presence of mono-allelic mutations of SLC26A4 in non-syndromic EVA patients is etiologically associated with this disorder. Additional genetic or environmental causes may be present in those patients and demand further investigation and consideration during the genetic diagnosis and counseling.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China; Department of Otorhinolaryngology-Head and Neck Surgery, Taizhou People's Hospital, Jiangsu Province, China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Yongchuan
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Penghui
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Longxia
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address: wuhao622@sina.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address: yangtfxl@sina.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
mesh_terms: D016022:Case-Control Studies; D002681:China; D003638:Deafness / Q000235:genetics*; D005819:Genetic Markers; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000002:abnormalities*
chemical_list: D005819:Genetic Markers; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters
keywords: Enlarged vestibular aqueduct; Genetic diagnosis; Mono-allelic mutation; SLC26A4