title: Functional characterization of wild-type and mutated pendrin (SLC26A4), the anion transporter involved in Pendred syndrome.
abstract: Pendred syndrome (PS) is the most frequent form of genetically related syndromic hearing loss, and is associated with mutations of pendrin, encoded by the SLC26A4 gene. This protein localizes to the cellular membrane and permits the exchange of anions between the cytosol and extracellular space. In the inner ear, pendrin conditions the endolymph, allowing for the proper function of sensory cells. Understanding the relationship between the genotype and phenotype of pendrin mutations would aid clinicians to better serve PS patients-however, little is known. Here, we summarize the available data concerning SLC26A4 mutations and how they relate to transporter function. The main findings suggest that all the truncation mutations tested annihilate pendrin function, and that the addition or omission of proline, or the addition or omission of charged amino acids in the sequence of SLC26A4 result in a substantial to dramatic reduction in pendrin function.
authors.affiliation: Institut of Pharmacology and Toxicology, Paracelsus Medical University, A-5020 Salzburg, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dossena
authors.forename: Simona
authors.initials: S
authors.lastname: Rodighiero
authors.forename: Valeria
authors.initials: V
authors.lastname: Vezzoli
authors.forename: Charity
authors.initials: C
authors.lastname: Nofziger
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Salvioni
authors.forename: Marta
authors.initials: M
authors.lastname: Boccazzi
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Grabmayer
authors.forename: Guido
authors.initials: G
authors.lastname: Bottà
authors.forename: Giuliano
authors.initials: G
authors.lastname: Meyer
authors.forename: Laura
authors.initials: L
authors.lastname: Fugazzola
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Markus
authors.initials: M
authors.lastname: Paulmichl
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D005838:Genotype; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism*; D000076988:Sulfate Transporters; D013577:Syndrome
chemical_list: D026901:Membrane Transport Proteins; D050505:Mutant Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters