Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere proteins. The most commonly mutated gene in familial HCM is:
- A TNNI3 encoding cardiac troponin I exclusively
- B MYH7 encoding beta-myosin heavy chain, or MYBPC3 encoding myosin binding protein C ✓
- C TTN encoding titin (largest sarcomere protein)
- D SCN5A encoding the cardiac sodium channel
Correct answer: B. MYH7 encoding beta-myosin heavy chain, or MYBPC3 encoding myosin binding protein C
Explanation
Approximately 60–70% of familial HCM cases harbor mutations in two genes: MYH7 (encoding beta-myosin heavy chain, ~35%) and MYBPC3 (encoding cardiac myosin binding protein C, ~35%). Both are thick-filament proteins. The mutations produce sarcomere hypercontractility through various gain-of-function and dominant-negative mechanisms. TNNI3 mutations account for a minority of cases. Titin (TTN) mutations predominantly cause dilated cardiomyopathy. SCN5A mutations cause Brugada syndrome and long QT syndrome.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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