title: Identification of a novel mutation in SLC26A4 gene in a Chinese family with enlarged vestibular aqueduct syndrome.
abstract: OBJECTIVE
  To investigate the genetic causes of hearing loss in a two generation Chinese family with enlarged vestibular aqueduct syndrome (EVAS).
  
  
  METHODS
  Clinical and genetic evaluations were conducted in a deaf proband and her normal-hearing parents. Sanger sequencing analysis of all the 21 exons, the exon-intron boundaries and the promoter in SLC26A4 gene was performed to detect the pathogenic mutations. PCR-restricted fragment length polymorphism (PCR-RFLP) was used to further identify the mutation. Phylogenetic analysis was carried out with multiple sequence alignment using BioEdit software. Three-dimensional (3D) modeling of the human wild-type and mutant SLC26A4 (NP_000432.1) was carried out using I-TASSER (http://zhanglab.ccmb.med.umich.edu/).
  
  
  RESULTS
  Clinical examinations showed that the proband suffered from typical features of sensorineural hearing loss with enlarged vestibular aqueduct. A novel nonsense mutation c.2118C>A (p.C706X) in exon 19 was identified in compound heterozygosity with the splice-site mutation c.919-2A>G in the proband by using Sanger sequencing. The mother was a heterozygous carrier of c.919-2A>G in intron 7, while the father was a heterozygous carrier of c.2118C>A. The mutation c.2118C>A was not found in 200 unrelated controls using Sanger sequencing. PCR-RFLP showed the PCR product of the proband was not digested at 2110 by Fau I because of the c.2118C>A mutation. 3D-structure modeling indicated that the mutation c.2118C>A resulted in a truncate Pendrin protein. Protein alignment indicated high conservation of p.C706 residue in healthy Homo, Nomascus, Pan, Macaca, Canis, Sus, Mus, Rattus, Cricetulus and Xenopus.
  
  
  CONCLUSIONS
  This study revealed a novel heterozygous mutation c.2118C>A (p.C706X) compound with c.919-2A>G in SLC26A4 gene in a patient with EVAS.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Fengguo
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China. Electronic address: sdphxl@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China; Shandong Provincial Key Laboratory of Otology, Jinan, PR China. Electronic address: wang.hb7585@hotmail.com.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002681:China; D018389:Codon, Nonsense; D005260:Female; D005819:Genetic Markers; D006319:Hearing Loss, Sensorineural / Q000208:ethnology / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D010375:Pedigree; D010802:Phylogeny; D000076988:Sulfate Transporters; D013577:Syndrome; D014723:Vestibular Aqueduct / Q000002:abnormalities*
chemical_list: D018389:Codon, Nonsense; D005819:Genetic Markers; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters
keywords: Chinese family; EVAS; Nonsense; Novel mutation; Pathogenicity; SLC26A4 gene