FUNCTIONAL ANALYSIS OF CONNEXIN MUTATIONS CAUSING GENETIC DEAFNESS

In developed countries deafness is mostly of genetic origin: the pathology is inherited, at least, in 60% of the cases. Many genes are involved in the different types of deafness (syndromic and non-syndromic). Non-syndromic hereditary deafness is mainly (80%) due to recessive mutations. It is believed that more than one hundred genes could be involved in hearing impairment. Recently, several of these genes have been identified. Despite the fact that more than 20 loci have been described for non-syndromic autosomal recessive deafness (DFNB), a single locus, DFNB1, accounts for a high proportion of the cases. The gene involved in this type of deafness, GJB2, encodes the gap junction protein Cx26, which belongs to the connexin family. Connexins are transmembrane proteins that form intercellular channels, and are expressed in many different tissues allowing rapid transport of ions and small molecules between neighboring cells. At least three more connexin genes are involved in deafness: GJB1 (Cx32), which is also responsible for the X-linked Charcot-Marie-Tooth disease; GJB6 (Cx30), which has recently been related to a dominant type of deafness in an Italian family; and GJB3 (Cx31), which is involved either in deafness or in skin disease depending on the location of the mutation. In the present research project, we propose to investigate further the role of Connexins in genetic deafness through an approach involving cell biology and functional studies. This will help us to understand the underlying pathogenic mechanisms at a molecular level and will provide preliminary information on new potential therapeutical approaches.