A 6-year-old boy has progressive proximal muscle weakness, calf pseudohypertrophy, and markedly elevated creatine kinase. Muscle biopsy shows necrosis and regeneration without inflammation. Immunohistochemistry demonstrates complete absence of membrane staining for a 427-kDa cytoskeletal protein. The inheritance pattern and protein involved are:

• A Autosomal recessive, sarcoglycan deficiency
• B X-linked recessive, merosin deficiency
• C Autosomal dominant, emerin deficiency
• D X-linked recessive, dystrophin deficiency ✓

Explanation

Duchenne muscular dystrophy results from out-of-frame deletions or mutations in the DMD gene at Xp21, causing complete absence of dystrophin, a 427-kDa protein linking the actin cytoskeleton to the dystrophin-glycoprotein complex. Loss destabilizes the sarcolemma, producing chronic myofiber necrosis. Inheritance is X-linked recessive, explaining onset in boys. Sarcoglycan deficiencies cause limb-girdle muscular dystrophies with preserved dystrophin staining. Emerin defects cause Emery-Dreifuss muscular dystrophy, an autosomal dominant nuclear envelope disease, and merosin (laminin alpha-2) deficiency causes a severe congenital muscular dystrophy.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.