title: A Novel Mutation in SLC26A4 Causes Nonsyndromic Autosomal Recessive Hearing Impairment.
abstract: Heterozygous mutations in GJB2 (MIM: 121011) encoding the gap junction protein connexin 26 are overrepresented in patient groups suffering from nonsyndromic sensorineural hearing impairment (HI) implying the involvement of additional genetic factors. Mutations in SLC26A4 (MIM: 605646), encoding the protein pendrin can cause both Pendred syndrome and autosomal recessive, nonsyndromic HI locus 4 type sensorineural HI (MIM: 600791).
  
  
  
  Aim of this study was to investigate the role of SLC26A4 coding mutations in a nonsyndromic hearing impairment (NSHI) patient group bearing heterozygous GJB2 35delG mutations.
  
  
  
  We analyzed the 20 coding exons of SLC26A4 in a group of patients (n = 15) bearing heterozygous 35delG mutations and exclusively suffering from congenital HI.
  
  
  
  In a case of bilateral congenital hearing loss we identified a rare, novel SLC26A4 exon 2 splice donor mutation (c.164+1delG) predicted to truncate pendrin in the first cytoplasmic domain, as a compound heterozygote with the pathogenic missense mutation c.1061T>C (p.354F>S; rs111033243).
  
  
  
  Screening for SLC26A4 mutations may identify the genetic causes of hearing loss in patients bearing heterozygous mutations in GJB2.
  
  
  
  SLC26A4 coding mutations are genetic causes for nonsyndromic HI in patients bearing heterozygous GJB2 35delG mutations.
authors.affiliation: *Department of Otorhinolaryngology, Head and Neck Surgery †Center of Anatomy and Cell Biology, Department for Cell and Developmental Biology ‡Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Graz, Graz §High Field MR Center, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Axel
authors.initials: A
authors.lastname: Wolf
authors.forename: Alexandra
authors.initials: A
authors.lastname: Frohne
authors.forename: Matthew
authors.initials: M
authors.lastname: Allen
authors.forename: Thomas
authors.initials: T
authors.lastname: Parzefall
authors.forename: Martin
authors.initials: M
authors.lastname: Koenighofer
authors.forename: Markus M
authors.initials: MM
authors.lastname: Schreiner
authors.forename: Christian
authors.initials: C
authors.lastname: Schoefer
authors.forename: Klemens
authors.initials: K
authors.lastname: Frei
authors.forename: Trevor
authors.initials: T
authors.lastname: Lucas
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D005091:Exons; D005260:Female; D006312:Hearing Loss, Bilateral / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D000076988:Sulfate Transporters; D055815:Young Adult
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26