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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Molecular and functional studies of 4 candidate loci in Pendred syndrome and nonsyndromic hearing loss / V. Cirello, C. Bazzini, V. Vezzoli, M. Muzza, S. Rodighiero, P. Castorina, A. Maffini, G. Botta, L. Persani, P. Beck-Peccoz, G. Meyer, L. Fugazzola. - In: MOLECULAR AND CELLULAR ENDOCRINOLOGY. - ISSN 0303-7207. - 351:2(2012), pp. 342-350.

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

V. Cirello;C. Bazzini;V. Vezzoli;M. Muzza;G. Botta;L. Persani;P. Beck-Peccoz;G. Meyer;L. Fugazzola
2012

Abstract

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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
EVA; FOXI1; KCNJ10; Pendred; SLC26A4
Settore MED/13 - Endocrinologia
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Article (author)
File in questo prodotto:
File Dimensione Formato  
Ciriello.pdf

non disponibili

Tipologia: Publisher's version/PDF
Dimensione 614.89 kB
Formato Adobe PDF
614.89 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/179093
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 16
social impact