Monday, 8 January | 2018 3:00 pm
Director, CNR Institute of Cell Biology and Neurobiology , International Campus “A. Buzzati-Traverso”, Monterotondo (RM), ITALY
Hearing impairment and skin diseases associated with connexin 26 mutations: etiopathogenesis and translational opportunities
(Host: M. Giacca)
The GJB2 gene has an estimated mutation prevalence of 3%in the general population. The encoded membrane protein,connexin 26 (Cx26), is expressed in the inner ear and the skin, together with the closely related connexin 30 (Cx30).Most GJB2 mutations cause nonsyndromic forms of hearingimpairment, which are prevalently autosomal recessive or,more rarely, autosomal dominant, and together affect ~1in 2000 newborn children. In addition, a certain number ofdominant GJB2 mutations cause syndromic forms associatedwith an array of rare skin diseases (Bart-Pumphrey syndrome;Hystrix-like ichthyosis with deafness; Keratitis-ichthyosis-deafness syndrome; Keratoderma, palmoplantar, with deafness; Vohwinkel syndrome).
Non-syndromic hearingimpairment is mainly associated with GJB2 mutations that cause complete loss of protein function, such as the highly prevalent 35delG, whereas most syndromic forms are causally linked to hyperactive mutant channels. Both classes of mutations represent highly challenging and virtually uncharted translational opportunities. I will discuss the etiopathogenesis of hearing loss linked to GJB2 mutations and highlight our attempts to treat relevant mouse models using recombinant adeno associated viral vectors with hightropism for inner ear non-sensory cells. I will also present a promising approach to treat skin disorders by contrasting channel hyperactivity with fully human monoclonal recombinant antibodies selected from a phage library.