학술논문
Functional Characterization of Wild-Type and a Mutated Form of SLC26A4 Identified in a Patient with Pendred Syndrome.
Document Type
Article
Author
Dossena, Silvia; Vezzoli, Valeria; Cerutti, Nadia; Bazzini, Claudia; Tosco, Marisa; Sironi, Chiara; Rodighiero, Simona; Meyer, Giuliano; Fascio, Umberto; Fürst, Johannes; Ritter, Markus; Fugazzola, Laura; Persani, Luca; Zorowka, Patrick; Storelli, Carlo; Beck-Peccoz, Paolo; Bottà, Guido; Paulmichl, Markus
Source
Subject
*PROTEINS
*GOITER
*CELLS
*DEAFNESS
*CELL membranes
*IODIDES
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*
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Language
ISSN
1015-8987
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 (SLC26A4S28R) 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 SLC26A4S28R we describe here, are consistent with the clinical phenotype observed in the patient from which the mutant was derived. [ABSTRACT FROM AUTHOR]