Duchenne/Becker Muscular Dystrophy
This research, which developed most actively in the mid-1980's and continues vigorously to the present, has been led in a most remarkable way by Dr. Louis Kunkel, Director of the Genetics Program and Associate Director of this IDDRC. Duchenne muscular dystrophy is a severe X-linked dystrophic myopathy; Becker muscular dystrophy is a phenotypically less severe disorder. In Duchenne muscular dystrophy a cognitive disturbance is present in all patients, such that as a group, IQ is distributed in a bell-shaped fashion but with a distinct shift of the curve to the left. The accomplishments of Kunkel and co-workers in the years leading to the 1995 renewal of this IDDRC were of profound importance (Adv. Hum. Gen., 1988; N. Engl. J. Med., 1988; Neuron, 1989; Nature, 1989; Nature, 1990; Am. J. Hum. Gen., 1991; J. Cell Biol., 1992; Nature Genetics, 1993; J. Cell Biol., 1995). Of particular note, Kunkel and his colleagues were the first to use restriction length polymorphisms to clone a disease gene. This work represents a landmark in the field of human genetics and sparked a revolution in genetics that has led to the positional cloning of dozens of human disease genes. The accomplishments of Kunkel and his colleagues that are relevant to muscular dystrophy include: cloning of the gene for Duchenne/Becker muscular dystrophy, discovery and characterization of the gene product dystrophin, demonstration that this protein is a cytoskeletal component in muscle, utilization of molecular analysis of specific defects in the dystrophin gene to establish molecular-phenotypic correlations in Duchenne muscular dystrophy, correction of the dystrophin defect in the MDX mouse by myoblast transfer, demonstration of dystrophin in postsynaptic elements of cerebral cortical neurons, and discovery of dystrophin-associated proteins. This groundbreaking work has provoked worldwide research which has focused on possible approaches to gene therapy in this devastating disease. The work continues in depth in new directions in this IDDRC.