D uchenne M uscular D ystrophy - GENETICS - The Cause and Cure By: Chaz B

What Is Muscular Dystrophy? Muscular Dystrophy is a group of inherited diseases in which the muscles that control movement progressively weaken. In some forms of this disease, the heart and other organs are also affected. Muscular Dystrophy can occur at different ages of a persons life, ranging from infancy to middle age or later. There are nine major forms of muscular dystrophy. The type of the disease is based in part on when in a person’s life muscular dystrophy appears, but it also depends on the severity of muscle weakness, which muscles are affected, the rate of symptom progression, and the way the disease arises.

Duchenne Muscular Dystrophy Duchenne muscular dystrophy (DMD) was first described by the French neurologist Dr. Guillaume Benjamin Amand Duchenne in the 1860’s. In DMD, boys begin to show signs of muscle weakness as early as age 3. The disease gradually weakens the voluntary muscles, such as those in the arms, legs and trunk. By the early teens or earlier, the boy’s heart and respiratory muscles also may be affected. Though DMD affects boys almost exclusively, in rare cases it can affect girls as well. (X-linked recessive disease)

The Signs of DMD The course of Duchenne Muscular Dystrophy is fairly predictable. Children with the disorder are often late in learning to walk. In toddlers, parents may notice enlarged calf muscles, or pseudohypertrophy. A preschooler with DMD may seem clumsy and often fall. Parents also may note that he has trouble getting up, climbing stairs or running. By school age, the child may walk on his toes or the balls of his feet, with a slightly rolling, unsteady gait. To try to keep his balance, the child will stick his belly out and put his shoulders back. He may also have difficulty raising his arms. Many children with DMD lose the ability to walk some time between the ages of 7 through 12. In the teen years, activities involving the arms, legs or trunk may require assistance or mechanical support.

The Anatomy of Skeletal Muscle

DMD Genetic Analysis The DMD gene is located on the short (p) arm of the X chromosome at position More precisely, the DMD gene is located from base pair 31,137,344 to base pair 33,357,725 on the X chromosome. Cytogenetic Location: Xp21.2 Molecular Location on the X chromosome: base pairs 31,137,344 to 33,357,725

DMD Genetic Analysis Exons are the portion of a gene which code for a protein, and a single gene can consist of many exons separated by stretches of DNA known as introns. The dystrophin gene has a total of 79 exons. Mutation in exons 45 through 52 result in either the production of a functionless truncated protein or in the production of a defective dystrophin protein that is quickly broken down, rather than undergoing processing to yield a mature functional dystrophin protein. It is this absence of a functioning dystrophin protein that results in the symptoms of DMD.

Possible Treatment? The antisense oligomer AVI-4658 works by binding to and blocking a specific sequence within exon 51 of the pre- messenger RNA. This causes the splicing machinery to skip the affected exons and yield a shortened dystrophin protein, missing a segment within it, which nevertheless includes the key functional portions at either end of the protein and thus restores most of the dystrophin functionality. The Muscular Dystrophy Campaign announced that the antisense oligonucleotide drug AVI-4658 had performed well in its second clinical trial in 19 boys with Duchenne Muscular Dystrophy (DMD)

Possible Treatment?

Works Cited "Dystrophin." Wikipedia, the Free Encyclopedia. Web. 28 Sept "Facts About Duchenne and Becker Muscular Dystrophies | MDA Publications." Welcome to MDA | Muscular Dystrophy Association. Web. 19 Sept Stout, Hilary. "Muscular Dystrophy Types & Causes of Each Form." WebMD - Better Information. Better Health. Web. 19 Sept