title: Functional characterization of pendrin mutations found in the Israeli and Palestinian populations.
abstract: BACKGROUND
  Pendrin is a transport protein exchanging chloride for other anions, such as iodide in the thyroid gland or bicarbonate in the inner ear. Mutations in the SLC26A4 gene encoding for pendrin are responsible for both syndromic (Pendred syndrome) and non-syndromic (non-syndromic enlarged vestibular aqueduct, EVA) hearing loss. Besides clinical and radiological assessments, molecular and functional studies are essential for the correct diagnosis of Pendred syndrome and non-syndromic EVA. While a broad spectrum of mutations found in the Caucasian population has been functionally characterized, little is known about mutations specifically occurring in the populations of the Middle East. Here we show the characterization of the ion transport activity of three pendrin mutations previously found in deaf patients with EVA in the Israeli Jewish and Palestinian Arab populations, i.e. V239D, G334V X335 and I487Y FSX39.
  
  
  METHODS
  Wild type and mutated pendrin allelic variants were functionally characterized in a heterologous over-expression system. The Cl(-)/I(-) and Cl(-)/OH(-) exchange activities were assessed by fluorometric methods suitable for measuring iodide fluxes and the intracellular pH.
  
  
  RESULTS
  Both the Cl(-)/I(-) and the Cl(-)/OH(-) exchange activities of pendrin V239D, G334V X335 and I487Y FSX39 were significantly reduced with respect to the wild type, with V239D displaying a residual iodide transport.
  
  
  CONCLUSIONS
  Functional assays confirmed the diagnosis of non-syndromic EVA due to SLC26A4 mutations performed by radiological and molecular tests in deaf patients belonging to the Israeli Jewish and Palestinian Arab populations. The new finding that the V239D mutation displays residual function suggests that the symptoms caused by this mutation could be ameliorated by a pendrin 'activator', if available.
authors: Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria. silvia.dossena@pmu.ac.at
authors: Silvia
authors: S
authors: Dossena
authors: Charity
authors: C
authors: Nofziger
authors: Zippora
authors: Z
authors: Brownstein
authors: Moien
authors: M
authors: Kanaan
authors: Karen B
authors: KB
authors: Avraham
authors: Markus
authors: M
authors: Paulmichl
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000838:Anions / Q000378:metabolism; D018912:Arabs / Q000235:genetics*; D034381:Hearing Loss / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D017136:Ion Transport; D007557:Israel; D007585:Jews / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D000076988:Sulfate Transporters
chemical_list: D000838:Anions; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters