Hela Azaiez - GJB2, GRXCR1

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Hearing impairment is the most frequent sensory defect in humans and is an economically and socially important cause of morbidity. Dramatic progress has been made in our understanding of the biology of hearing and deafness through the mapping of more than 120 loci and the identification of more than 41 genes. My research work focuses on the identification of novel genes/mutations responsible for hereditary hearing loss at the DFNB1, DFNB25, DFNB33 and OTSC1 (Otosclerosis) loci.

Mutations in GJB2 and GJB6 genes at the DFNB1 locus account for half of all severe-to-profound recessive deafness in several ethnic groups. However mutation screening of GJB2 in individuals whose hearing loss is consistent with GJB2 deafness reveals a high prevalence of monoallelic mutations implying the existence of yet-to-be-discovered mutations in trans. We hypothesized that these mutations lie in a regulatory element (enhancers, repressors or insulators) that is required for spatiotemporal and quantitative control of GJB2 and/or GJB6 expression in the inner ear. To identify these regulatory regions and putative mutations, we use a battery of tools including comparative genomics, association studies, fine tiling array CGH, 454 sequencing…

In order to identify novel genes at the DFNB25, DFNB33 and OTSC1 loci, we are screening candidate genes that have been chosen based on the existence of animal model, expression profiles and putative functions.

The identification of genes associated with deafness is an important step towards a better understanding of the molecular mechanisms of hearing. The short term benefits this knowledge provides are being realized in clinical medicine, where the use of genetic screening for deafness has changed the evaluation of the deaf person. In the long term, this knowledge will result in the development of novel treatment options for deafness.