title: Screening of the SLC17A8 gene as a causative factor for autosomal dominant non-syndromic hearing loss in Koreans.
abstract: BACKGROUND
  One of the causes of sensorineural hearing loss (SNHL) is degeneration of the inner hair cells in the organ of Corti in the cochlea. The SLC17A8 (solute carrier family 17, member 8) gene encodes vesicular glutamate transporter 3 (VGLUT3), and among its isoforms (VGLUT1-3), only VGLUT3 is expressed selectively in the inner hair cells (IHCs). VGLUT3 transports the neurotransmitter glutamate into the synaptic vesicles of the IHCs. Mutation of the SLC17A8 gene is reported to be associated with DFNA25 (deafness, autosomal dominant 25), an autosomal dominant non-syndromic hearing loss (ADNSHL) in humans.
  
  
  METHODS
  In this study, we performed a genetic analysis of 87 unrelated Korean patients with ADNSHL to determine whether the SLC17A8 gene affects hearing ability in the Korean population.
  
  
  RESULTS
  We found a novel heterozygous frameshift mutation, 2 non-synonymous variations, and a synonymous variation. The novel frameshift mutation, p.M206Nfs*4, in which methionine is changed to asparagine at amino acid position 206, resulted in a termination codon at amino acid position 209. This alteration is predicted to encode a truncated protein lacking transmembrane domains 5 to 12. This mutation is located in a highly conserved region in VGLUT3 across multiple amino acid alignments in different vertebrate species, but it was not detected in 100 unrelated controls who had normal hearing ability. The results from our study suggest that the p.M206Nfs*4 mutation in the SLC17A8 gene is likely a pathogenic mutation that causes ADNSHL.
  
  
  CONCLUSIONS
  Our findings can facilitate the prediction of the primary cause of ADNSHL in Korean patients.
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, 41566, South Korea. runa0927@knu.ac.kr.
authors.forename: Nari
authors.initials: N
authors.lastname: Ryu
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, 41566, South Korea. moongigi3@knu.ac.kr.
authors.forename: Borum
authors.initials: B
authors.lastname: Sagong
authors.affiliation: Soree Ear Clinics, Seoul, 06068, South Korea. hjparkmd@hanmail.net.
authors.forename: Hong-Joon
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, 41566, South Korea. minaaa@knu.ac.kr.|School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, South Korea. minaaa@knu.ac.kr.
authors.forename: Min-A
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea. kylee@knu.ac.kr.
authors.forename: Kyu-Yup
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, 03722, South Korea. jychoi@yuhs.ac.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, 41566, South Korea. kimuk@knu.ac.kr.|School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, South Korea. kimuk@knu.ac.kr.
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D016368:Frameshift Mutation; D005820:Genetic Testing; D023281:Genomics; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D056910:Republic of Korea; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D050496:Vesicular Glutamate Transport Proteins / Q000235:genetics*
chemical_list: C460879:SLC17A8 protein, human; D050496:Vesicular Glutamate Transport Proteins