Usher Syndrome Review and USH1C Research Update, Jennifer J. Lentz, PhD скачать в хорошем качестве

Usher Syndrome Review and USH1C Research Update, Jennifer J. Lentz, PhD

Approximately 2.5% of Usher syndrome (Usher, USH) is caused by mutations in the USH1C gene, which encodes the protein harmonin. This presentation gives an overview of one specific mutation (216A) that accounts for nearly all Type 1 cases of Usher in Acadian populations of Louisiana, USA and Canada. Aberrant splicing at the 216A position causes the deletion of 35 base pairs from the mRNA and a frame shift in the transcript, which produces a truncated harmonin protein. We created a unique mouse model of USH1C by knocking-in the human 216A mutation. The USH1C mice show hearing, balance, and visual dysfunction similar to patients. We use this USH1C mouse model to develop therapies aimed at preventing or curing the disease. Recently, we developed antisense and gene therapies that restore hearing, balance, and vision in the USH1C mice. Currently, we are optimizing these therapeutic strategies for the treatment of visual loss and imbalance in USH1C patients. Additionally, our research aims to improve our understanding of the molecular epidemiology and natural medical history of USH1C throughout the world. We conduct several USH1C natural history studies (NHS) including a retrospective analysis of medical data, and prospective analyses of the natural history of visual loss and imbalance. Currently, a total of 103 study participants, ranging in age from 18 months – 93 years have been enrolled from our clinics at LSUHSC, clinical colleagues throughout the US, Canada, and Europe, and contacts at patient advocacy groups (Usher 2020, Ush One See, and Usher Syndrome Coalition Foundations). Molecular diagnosis of Usher syndrome is confirmed by genetic testing performed either by the referring physician or confirmed by us through a collaboration with a clinical laboratory (Dr. Edwin Stone, Usher Project, University of Iowa). The long-term goals of our studies are to develop new therapies for USH1C, and identify patients and clinical tests that could be used to guide a future clinical trial.