title: Efficient molecular genetic diagnosis of enlarged vestibular aqueducts in East Asians.
abstract: BACKGROUND
  Enlargement of the vestibular aqueduct (EVA) is a commonly detected inner ear anomaly related to hearing loss and often associated with mutations of SLC26A4 encoding pendrin, a transmembrane exchanger of Cl(-), I(-), and HCO(3)(-). Here we describe the phenotypes of 27 Korean EVA subjects and their SLC26A4 genotypes determined by bidirectional nucleotide sequencing.
  
  
  RESULTS
  The detected variants include two novel missense substitutions (p.V138L and p.P542R). We characterized the ability of p.V138L and p.P542R pendrin products to traffic to the plasma membrane in COS-7 cells and to transport Cl(-), I(-), and HCO(3)(-) in Xenopus oocytes. The results indicate that p.P542R is a benign polymorphic variant, whereas p.V138L is a pathogenic mutation. Since this and other studies of East Asian EVA cohorts show that the majority of SLC26A4 mutations affect either or both of two amplicons (exons 7-8 and 19), we developed a hierarchical protocol that integrates direct sequencing with denaturing high-performance liquid chromatography analyses for detection of SLC26A4 mutations in these populations. We validated the cost efficiency of the integrated protocol by a simulated screen of published East Asian EVA cohorts with known SLC26A4 genotypes.
  
  
  CONCLUSIONS
  Our study further defines the spectrum of SLC26A4 mutations among East Asians and demonstrates a rapid and efficient protocol for their detection.
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Byung Yoon
authors: BY
authors: Choi
authors: Andrew K
authors: AK
authors: Stewart
authors: Katherine K
authors: KK
authors: Nishimura
authors: Won Jae
authors: WJ
authors: Cha
authors: Moon-Woo
authors: MW
authors: Seong
authors: Sung Sup
authors: SS
authors: Park
authors: Seung Won
authors: SW
authors: Kim
authors: Yang Sook
authors: YS
authors: Chun
authors: Jong Woo
authors: JW
authors: Chung
authors: Shi-Nae
authors: SN
authors: Park
authors: Sun O
authors: SO
authors: Chang
authors: Chong-Sun
authors: CS
authors: Kim
authors: Seth L
authors: SL
authors: Alper
authors: Andrew J
authors: AJ
authors: Griffith
authors: Seung-Ha
authors: SH
authors: Oh
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D025202:Molecular Diagnostic Techniques; D020125:Mutation, Missense; D056910:Republic of Korea; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000473:pathology*; D015837:Vestibular Diseases / Q000175:diagnosis* / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters