Molecular and functional studies of 4 candidate loci in Pendred syndrome and nonsyndromic hearing loss

Valentina Cirello, Claudia Bazzini, Valeria Vezzoli, Marina Muzza, Simona Rodighiero, Pierangela Castorina, Antonia Maffini, Guido Bottà, Luca Persani, Paolo Beck-Peccoz, Giuliano Meyer, Laura Fugazzola

Research output: Contribution to journalArticlepeer-review


Patients with PS or non-syndromic deafness were submitted to genetic/functional analyzes of SLC26A4, of its binding domain for FOXI1 (FOXI1-DBD). , of the transcription activator FOXI1, and of the potassium channel KCNJ10. SLC26A4 was the most frequently mutated gene. An altered intracellular localization with immunocytochemistry, and a hampered maturation process were demonstrated for two novel SLC26A4 variants. Biochemical and immunocytochemical analyzes led to the development of a more sensitive fluorometric functional assay able to reveal the partial loss-of-function of SLC26A4 mutations. A novel missense variant was found in FOXI1 gene, though functional analysis showed no significant impairment in the transcriptional activation of SLC26A4. Finally, 3 patients were found to harbor a variant in KCNJ10, which was classified as polymorphism.The novelty of the study resides in the analysis of all the 4 candidate genetic loci linked to PS/non-syndromic deafness, and in the precise definition of the thyroid phenotype. PS was invariably associated with biallelic mutations of SLC26A4, whereas the genetic origin of non-syndromic deafness remained largely undetermined, since monoallelic SLC26A4 variants accounted for one fourth of the cases and FOXI1 and KCNJ10 were not involved in this series.

Original languageEnglish
Pages (from-to)342-350
Number of pages9
JournalMolecular and Cellular Endocrinology
Issue number2
Publication statusPublished - Apr 4 2012


  • EVA
  • FOXI1
  • KCNJ10
  • Pendred
  • SLC26A4

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry


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