title: Functional characterization of wild-type and a mutated form of SLC26A4 identified in a patient with Pendred syndrome.
abstract: BACKGROUND
  Malfunction of the SLC26A4 protein leads to prelingual deafness often associated with mild thyroid dysfunction and goiter. It is assumed that SLC26A4 acts as a chloride/anion exchanger responsible for the iodide organification in the thyroid gland, and conditioning of the endolymphatic fluid in the inner ear.
  
  
  METHODS
  Chloride uptake studies were made using HEK293-Phoenix cells expressing human wild type SLC26A4 (pendrin) and a mutant (SLC26A4(S28R)) we recently described in a patient with hypothyroidism, goiter and sensorineural hearing loss.
  
  
  RESULTS
  Experiments are summarized showing the functional characterization of wild type SLC26A4 and a mutant (S28R), which we described recently. This mutant protein is transposed towards the cell membrane, however, its transport capability is markedly reduced if compared to wild-type SLC26A4. Furthermore, we show that the SLC26A4 induced chloride uptake in HEK293-Phoenix cells competes with iodide, and, in addition, that the chloride uptake can be blocked by NPPB and niflumic acid, whereas DIDS is ineffective.
  
  
  CONCLUSIONS
  The functional characteristics of SLC26A4(S28R) we describe here, are consistent with the clinical phenotype observed in the patient from which the mutant was derived.
authors.affiliation: Department of Biomolecular Sciences and Biotechnology, Università degli Studi di Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dossena
authors.forename: Valeria
authors.initials: V
authors.lastname: Vezzoli
authors.forename: Nadia
authors.initials: N
authors.lastname: Cerutti
authors.forename: Claudia
authors.initials: C
authors.lastname: Bazzini
authors.forename: Marisa
authors.initials: M
authors.lastname: Tosco
authors.forename: Chiara
authors.initials: C
authors.lastname: Sironi
authors.forename: Simona
authors.initials: S
authors.lastname: Rodighiero
authors.forename: Giuliano
authors.initials: G
authors.lastname: Meyer
authors.forename: Umberto
authors.initials: U
authors.lastname: Fascio
authors.forename: Johannes
authors.initials: J
authors.lastname: Fürst
authors.forename: Markus
authors.initials: M
authors.lastname: Ritter
authors.forename: Laura
authors.initials: L
authors.lastname: Fugazzola
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
authors.forename: Patrick
authors.initials: P
authors.lastname: Zorowka
authors.forename: Carlo
authors.initials: C
authors.lastname: Storelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Guido
authors.initials: G
authors.lastname: Bottà
authors.forename: Markus
authors.initials: M
authors.lastname: Paulmichl
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006042:Goiter / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007454:Iodides / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D009544:Niflumic Acid / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D000076988:Sulfate Transporters; D013577:Syndrome
chemical_list: D002712:Chlorides; D007454:Iodides; D026901:Membrane Transport Proteins; D009579:Nitrobenzoates; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D009544:Niflumic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid