Describe Duchenne muscular dystrophy and the molecular basis.

• A. It is caused by a deficiency of dystrophin that prevents cross-bridge formation.
• B. X-linked mutation in the dystrophin gene leading to loss of dystrophin, destabilizing the muscle cell membrane during contraction and progressive weakness.
• C. Autoimmune destruction of acetylcholine receptors at the NMJ.
• D. Mutation in the myosin heavy chain that reduces contractility.

Answer: (B)

Duchenne muscular dystrophy happens when dystrophin is missing because of an X-linked mutation in the dystrophin gene. Dystrophin normally acts as a bridge that connects the internal cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the dystrophin-glycoprotein complex, helping to stabilize the muscle fiber’s membrane during contraction. Without dystrophin, the sarcolemma becomes fragile and tears as the muscle shortens and contracts, allowing calcium to flood into the cell. This calcium overload activates enzymes that damage proteins, leading to myofiber death and replacement of muscle tissue with fat and fibrous tissue. The result is progressive weakness, starting in the proximal muscles, and calves that appear enlarged due to pseudohypertrophy. The inheritance pattern is X-linked, so affected individuals are typically boys with carrier mothers. This description aligns best with the explanation that the disease stems from an X-linked loss of dystrophin that destabilizes the muscle membrane during contraction, causing progressive weakness.