Stepping Forward With MD: Current Research on Five Common Types

The muscular dystrophies (MDs) encompass a range of genetic diseases characterized primarily by skeletal muscle wasting, with possible weakening of the heart. Clinical manifestations of these diseases have been documented for more than a century; however, the molecular defects that cause MD were only discovered in the last twenty years. Some forms of the disease, including Duchenne muscular dystrophy (DMD) and congenital muscular dystrophy (CMD), result from mutations in genes coding for proteins crucial to muscle cell structure. In these forms of MD, symptoms result from a deficiency of dystrophin or an associated protein in the dystrophin-glycoprotein complex (DGC), a structure that preserves function of normal muscle fibers. Another form of MD, limb-girdle muscular dystrophy (LGMD), is caused by a mutation encoding a protein component of the plasma membrane. Still other forms of the disease exist; fascioscapulohumeral muscular dystrophy (FSHD) and myotonic dystrophy (DM) result from nucleotide repeats and silencer deletions on skeletal muscle genes, respectively. In these forms of MD, symptoms are due to abnormal pre-mRNA splicing. This paper reviews current literature on the molecular basis and therapeutic strategies of five types of MD