title: Functional characterization of a novel Cx26 (T55N) mutation associated to non-syndromic hearing loss.
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.
authors.affiliation: Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, University of Trieste, Trieste, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Melchionda
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bicego
authors.forename: Elio
authors.initials: E
authors.lastname: Marciano
authors.forename: Annamaria
authors.initials: A
authors.lastname: Franzè
authors.forename: Marcello
authors.initials: M
authors.lastname: Morgutti
authors.forename: Grazia
authors.initials: G
authors.lastname: Bortone
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.forename: Paola
authors.initials: P
authors.lastname: D'Andrea
mesh_terms: D001483:Base Sequence; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism*; D004252:DNA Mutational Analysis / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D034381:Hearing Loss / Q000151:congenital / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007558:Italy; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013577:Syndrome
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26