Muscle Disorders!

High School? Wow.

Together myosin, actin, tropomyosin, and troponin make up over three-quarters of the protein in muscle fibers. Some two dozen other proteins make up the rest. These serve such functions as attaching and organizing the filaments in the sarcomere and connecting the sarcomeres to the plasma membrane and the extracellular matrix. Mutations in the genes encoding these proteins may produce defective proteins and resulting defects in the muscles. Among the most common of the muscular dystrophies are those caused by mutations in the gene for dystrophin. The gene for dystrophin is huge, containing 79 exons spread out over 2.4 million base pairs of DNA. Thus this single gene represents about 0.1% of the entire human genome (3 x 109 bp) and is almost half the size of the entire genome of E. coli!

Duchenne muscular dystrophy (DMD)

Deletions or nonsense mutations that cause a frameshift usually introduce premature termination codons (PTCs) in the resulting mRNA. Thus at best only a fragment of dystrophin is synthesized and DMD, a very severe form of the disease, results.

The gene for dystrophin is on the X chromosome, so these two diseases strike males in a typical X-linked pattern of inheritance.

Treatment

Deletions of one or more exons in the huge dystrophin gene are the cause of most of the cases of DMD. Exon 50 is a particularly notorious offender. When it is deleted, splicing of the pre-mRNA introduces a frameshift which then introduces a premature termination codon resulting in no functional dystrophin synthesized ("B"). However, antisense oligodeoxynucleotide (ODNs) targeted to exon 51 cause the splicing mechanism to skip over it resulting in the stitching together of exons 49 and 52. This restores the correct reading frame so that only a slightly-altered version of dystrophin is produced, i.e., a BMD-type dystrophin ("C"). Not only does the antisense ODN treatment work in cell culture, but injecting leg muscles of four young DMD patients in the Netherlands with the same antisense ODN caused their muscle to synthesize small amounts of dystrophin. However, the area treated was too small to increase the strength of the muscle.

See Attachment

There is no known cure for muscular dystrophy, although significant headway is being made with antisense oligonucleotides. Inactivity (such as bed rest and even sitting for long periods) can worsen the disease. Physical therapy, occupational therapy, orthotic intervention (e.g., ankle-foot orthosis), speech therapy and orthopedic instruments (e.g., wheelchairs and standing frames) may be helpful.

The disease affects muscles. So technically all the muscles in your body, including the heart, endocrine organs, eyes, and gastrointestinal tract - skeletal muscles.