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.

Functional characterization of wild-type and a mutated form of SLC26A4 identified in a patient with pendred syndrome / S. Dossena, V. Vezzoli, N. Cerutti, C. Bazzini, M. Tosco, C. Sironi, S. Rodighiero, G. Meyer, U. Fascio, J. Fürst, M. Ritter, L. Fugazzola, L. Persani, P. Zorowka, C. Storelli, P. Beck-Peccoz, G. Bottà, M. Paulmichl. - In: CELLULAR PHYSIOLOGY AND BIOCHEMISTRY. - ISSN 1015-8987. - 17:5-6(2006), pp. 245-256. [10.1159/000094137]

Functional characterization of wild-type and a mutated form of SLC26A4 identified in a patient with pendred syndrome

S. Dossena;V. Vezzoli;N. Cerutti;C. Bazzini;M. Tosco;C. Sironi;S. Rodighiero;G. Meyer;U. Fascio;L. Fugazzola;L. Persani;P. Beck-Peccoz;G. Bottà;M. Paulmichl
2006

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.
pendred syndrome; SLC26A4; chloride/bicarbonate exchanger; chloride uptake; ion transport; NPPB; DIDS; niflumic acid
Settore MED/13 - Endocrinologia
Settore BIO/09 - Fisiologia
2006
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/24254
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