title: Hearing loss: frequency and functional studies of the most common connexin26 alleles.
abstract: Mutations in the GJB2 gene, encoding the gap-junction channel protein connexin 26, account for the majority of recessive forms and some of the dominant cases of deafness. Here, we report the frequency of GJB2 alleles in the Italian population affected by hearing loss and the functional analysis of six missense mutations. Genetic studies indicate that, apart from the common 35delG, only few additional mutations can be detected with a significant frequency in our population. Transfection of communication-incompetent HeLa cells with Cx26 missense mutations revealed three distinct classes of functional deficits in terms of protein expression, subcellular localisation and/or functional activity. Moreover, the M34T mutant acted as a dominant inhibitor of wild-type Cx26 channel activity when the two proteins were co-expressed in a manner mimicking a heterozygous genotype. These data support the hypothesis of a functional role for M34T as a dominant allele and represent a further step towards a complete understanding of the role of GJB2 in causing hearing loss.
authors.affiliation: Dipartimento di Biochimica, Biofisica e Chimica delle, Macromolecole, University of Trieste, via Licio Giorgieri 1, I-34127 Trieste, Italy. dandrea@bbcm.univ.trieste.it
authors.forename: Paola
authors.initials: P
authors.lastname: D'Andrea
authors.forename: Valentina
authors.initials: V
authors.lastname: Veronesi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bicego
authors.forename: Salvatore
authors.initials: S
authors.lastname: Melchionda
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Enzo
authors.initials: E
authors.lastname: Di Iorio
authors.forename: Roberto
authors.initials: R
authors.lastname: Bruzzone
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
mesh_terms: D000483:Alleles; D000072259:Connexin 26; D017630:Connexins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D003638:Deafness / Q000235:genetics*; D005787:Gene Frequency; D006367:HeLa Cells; D006801:Humans; D007558:Italy; D009154:Mutation; D020125:Mutation, Missense; D011487:Protein Conformation
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26