Rare Diseases Symptoms Automatic Extraction

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 SLC26A4 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. V239D, G334V X335 and I487Y FSX39.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 V239D, G334V X335 and I487Y FSX39 were significantly reduced with respect to the wild type, with V239D displaying a residual iodide transport.Functional assays confirmed the diagnosis of non-syndromic EVA due to SLC26A4 mutations performed by radiological and molecular tests in deaf patients belonging to the Israeli Jewish and Palestinian Arab populations. The new finding that the V239D mutation displays residual function suggests that the symptoms caused by this mutation could be ameliorated by a pendrin 'activator', if available.

Diseases presenting "broad spectrum" symptom

  • adrenomyeloneuropathy
  • cushing syndrome
  • cystinuria
  • dentinogenesis imperfecta
  • dystrophic epidermolysis bullosa
  • epidermolysis bullosa simplex
  • focal myositis
  • hereditary cerebral hemorrhage with amyloidosis
  • hodgkin lymphoma, classical
  • kabuki syndrome
  • kallmann syndrome
  • krabbe disease
  • neonatal adrenoleukodystrophy
  • omenn syndrome
  • pendred syndrome
  • pleomorphic liposarcoma
  • triple a syndrome
  • waldenström macroglobulinemia

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