College of Physicians and Surgeons
The nuclear membranes and associated nuclear lamina network separate chromatin from the cytoplasmic compartment. Mutations in emerin, a transmembrane protein of the inner nuclear membrane, have been found to be the cause of the X-linked form of Emery-Dreifuss muscular dystrophy (EDMD). The principal applicant of this grant proposal recently identified mutations in the gene LMNA on chromosomes 1q11-23 in patients with an autosomal-dominant form of EDMD and in patients with limb-girdle muscular dystrophy, type 1B. The LMNA gene encodes, through alternative RNA splicing, lamins A and C, two major intermediate filament proteins that compose the lamina. The goal of this proposal is the elucidation of the mechanisms linking mutations in the ubiquitously expressed lamins A and C to a dysfunction of skeletal and cardiac muscles. This multidisciplinary project combines fundamental and clinical genetic approaches. The international collaboration will involve four laboratories from the United States, France, Norway, and Japan.
Project Leader/Principal Investigator
Department of Anatomy and Cell Biology
Human Frontiers Science Project (HFSP)
Institut National de la Sante et de la Recherche Medicale (INSERM)
Groupe Hospitalier Pitie-Salpetriere