In Duchenne muscular dystrophy, the absence of dystrophin leads to skeletal muscle fibre necrosis. The immediate consequence of dystrophin loss is:

• A Loss of utrophin isoform from neuromuscular junction, uncoupling excitation-contraction
• B Mitochondrial fusion defect causing ATP depletion during repetitive contraction
• C Failure of sarcolemmal integrity causing calcium influx and activation of proteases ✓
• D Upregulation of myostatin inhibiting satellite cell differentiation and repair

Explanation

Dystrophin links the intracellular actin cytoskeleton to the extracellular matrix via the dystrophin-associated protein complex (DAPC). Its absence destabilises the sarcolemma during contraction, causing microtears and calcium influx through mechanically injured membrane. Elevated intracellular calcium activates calpains (proteases) and phospholipases, triggering fibre necrosis. Satellite cell-mediated regeneration eventually becomes exhausted, and fibrotic replacement ensues. Utrophin compensates partially at the NMJ but cannot replace dystrophin's structural role. Myostatin and mitochondrial defects are secondary features, not the primary pathogenic mechanism.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.