Functional characterization of pendrin mutations found in the Israeli and Palestinian populations.

[pendred syndrome]

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 SLC 26 A 4 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 . V 239 D , G 334 V X 335 and I 487 Y FSX 39 .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 .Both the Cl (-)/I (-) and the Cl (-)/OH (-) exchange activities of pendrin V 239 D , G 334 V X 335 and I 487 Y FSX 39 were significantly reduced with respect to the wild type , with V 239 D displaying a residual iodide transport .Functional assays confirmed the diagnosis of non-syndromic EVA due to SLC 26 A 4 mutations performed by radiological and molecular tests in deaf patients belonging to the Israeli Jewish and Palestinian Arab populations . The new finding that the V 239 D mutation displays residual function suggests that the symptoms caused by this mutation could be ameliorated by a pendrin 'activator ', if available .

Diseases
Validation

Diseases presenting "enlarged vestibular aqueduct" symptom

pendred syndrome

This symptom has already been validated