ALTERATION OF THE BIOLOGICAL FUNCTIONS OF DRF1 AND DRF2 BY PATHOGENIC FAMILIAL MUTATIONS

Hereditary deafness and Premature ovarian failure (POF) are two important syndromesthat can be caused by environmental or unknown factors, autoimmune reactionsand genetic mutations . Patients with hereditary deafness experiencedebilitating and progressive hearing loss. Women with POF, which occurs inapproximately 1% of women in Western populations, experience menopause priorto age 40 years, while the median age at menopause of the normal femalepopulation is about 51 years.DFNA1, a particular form of hereditary deafness, and some genetic forms ofPOF are caused by mutations in two similar genes, DRF1 and DRF2,respectively. In this proposal, we plan to study the normal function ofDRF1 and DRF2. Next, we will address whether mutations in DRF1 and DRF2 thatcause DFNA1 and POF respectively, alter the normal functions of these genes. Thesestudies should unveil why and how the pathological genetic mutations in DRF1and DRF2 subvert the normal cellular functions that can cause these diseases.This knowledge will provide a platform to develop strategies to prevent andcure these cases of hereditary deafness and premature menopause. Inaddition, it is likely that these strategies could be extended to other formof deafness and premature ovarian failure that have different etiology butsimilar pathogenic mechanisms.