GJB2 Gene Mutations in Syndromic Skin Diseases with Sensorineural Hearing Loss
Pp. 30-46 (17)
Sandra Iossa, Elio Marciano and Annamaria Franzé
Hearing loss is a very diffuse disease in the population and many cases are
associated to genetic causes. Most of the identified mutations have been identified in the
GJB2 gene encoding connexin 26, a transmembrane protein that is a constituent of
fundamental structures (gap junctions channels) involved in molecules (ions and small
metabolites) exchanges between cells. It has been demonstrated that GJB2 mutations
are causative for different forms of hearing impairment, non-syndromic forms: recessive
(DFNB1) and sometimes dominant (DFNA3) as well as syndromic dominant forms
with hearing impairment associated to several types of epidermis problems. Connexin
26, in fact, has a relevant role in inner ear functioning but in the skin too, where
connexins 26 has been demonstrated to participate in regulation of growth and
differentiation of skin. As well as for many cases of hearing loss, skin phenotypes
described for connexin 26 mutations are highly variable. Reasons for this high
phenotypic variability are actually not clear. This review provides an overview of recent
findings concerning pathogenesis of syndromic deafness imputable to GJB2 mutations
with an emphasis on relevant clinical genotype-phenotype correlations. Effects of some
mutations on channels function and the relevant role of the hemichannel are discussed.
BPS, Calcium Uptake, Cellular Death, Cellular Trafficking, Connexin
26, Deafness, Dominant Mutation, EKV, Epidermis, Gap Junction, Genotype-
Phenotype Correlation, GJB2, Hearing Loss, Hemichannel, HID, Keratoderma,
KID, Phenotypic Variability, PPK, Skin, Vohwinkel Syndrome.
Unità di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive e Odontostomatologiche, Università degli Studi di Napoli “Federico II”, Via Pansini 5, 80131 Napoli, Italy.