Gene mutations: Types of muscular dystrophy

Muscular dystrophy (MD) refers to a group of genetic disorders characterized by progressive muscle degeneration and weakness. It is caused by mutations in the genes responsible for the structure and function of muscles. MD can affect people of all ages, and its severity and progression vary widely.

Duchenne muscular dystrophy (DMD) is an X-linked recessive form of degenerative dystrophy usually diagnosed in early childhood (around ages 3 to 5). DMD is caused by the abnormal expression of dystrophin, a 500-kDa protein that helps to maintain the structural integrity of muscle fibers. In DMD patients, various deletions in the dystrophin gene lead to either a defective form of dystrophin or a complete lack of dystrophin. Scientists are able to identify sequences corresponding to the region of DNA that contains the deletion; they do this by using DNA probes made from the normal dystrophin sequence, which they hybridize with DNA from normal individuals and DMD patients. The deletions occur at different locations in each patient, suggesting that they occur de novo. The most severe and common deletion is located in the center of the locus. The sequence of the deletion in the coding strand has been determined to be 5’—GCCATAGAGCGA—3’.

Myotonic dystrophy, another common form of muscular dystrophy, usually presents in adulthood and results in progressive weakness and muscle wasting. Many people with this disorder suffer from myotonia, or prolonged muscle contractions, and are not able to relax their muscles after use. This dystrophy can affect voluntary skeletal muscle as well as involuntary cardiac and smooth muscle. There are two major types of myotonic dystrophy, which are referred to as type 1 (DM1) and type 2 (DM2). DM1 usually results from an increase in the number of CTG triplet repeats in the DMPK gene, which encodes for myotonic dystrophy protein kinase (DMPK), with a larger number of inserted repeats leading to more significant symptoms. DM2, on the other hand, results from an increase in the number of CCTG repeats in the intron of the CNBP gene, which codes for zinc finger protein 9 (ZNF9). Myotonic dystrophy can be difficult to diagnose as it presents similarly to other defects in the muscular system, and it is also challenging to treat due to its multi-systemic effects.