Mutations of the GJB2 gene, encoding connexin 26, are the most common cause of hereditary congenital hearing loss in many countries and account for up to 50% of cases of autosomal-recessive non-syndromic deafness. By contrast, only a few GJB2 mutations have been reported to cause an autosomal-dominant form of non-syndromic deafness. Here, we report a family from Southern Italy affected by non-syndromic autosomal dominant post-lingual hearing loss, due to a novel missense mutation in the GJB2 gene, a threonine to asparagine amino acid substitution at codon 55 (T55N). Functional studies indicated that the mutation T55N produces a protein that, although expressed to levels similar to those of the wt counterpart, is deeply impaired in its intracellular trafficking and fails to reach the plasma membrane. The mutation T55N is located at the apex of the first extracellular loop of the protein, a region suggested to play a role in protein targeting and a site for other two mutations, G59A and D66H, causing dominant forms of deafness.

Functional characterization of a novel Cx26 (T55N) mutation associated to non-syndromic hearing loss / Melchionda, S; Bicego, M; Marciano, Elio; Franze', Annamaria; Morgutti, M; Bortone, G; Zelante, L; Carella, M; D'Andrea, P.. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - STAMPA. - 337:3(2005), pp. 799-805. [10.1016/j.bbrc.2005.09.116]

Functional characterization of a novel Cx26 (T55N) mutation associated to non-syndromic hearing loss.

MARCIANO, ELIO;FRANZE', Annamaria;
2005

Abstract

Mutations of the GJB2 gene, encoding connexin 26, are the most common cause of hereditary congenital hearing loss in many countries and account for up to 50% of cases of autosomal-recessive non-syndromic deafness. By contrast, only a few GJB2 mutations have been reported to cause an autosomal-dominant form of non-syndromic deafness. Here, we report a family from Southern Italy affected by non-syndromic autosomal dominant post-lingual hearing loss, due to a novel missense mutation in the GJB2 gene, a threonine to asparagine amino acid substitution at codon 55 (T55N). Functional studies indicated that the mutation T55N produces a protein that, although expressed to levels similar to those of the wt counterpart, is deeply impaired in its intracellular trafficking and fails to reach the plasma membrane. The mutation T55N is located at the apex of the first extracellular loop of the protein, a region suggested to play a role in protein targeting and a site for other two mutations, G59A and D66H, causing dominant forms of deafness.
2005
Functional characterization of a novel Cx26 (T55N) mutation associated to non-syndromic hearing loss / Melchionda, S; Bicego, M; Marciano, Elio; Franze', Annamaria; Morgutti, M; Bortone, G; Zelante, L; Carella, M; D'Andrea, P.. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - STAMPA. - 337:3(2005), pp. 799-805. [10.1016/j.bbrc.2005.09.116]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/304050
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