In hypertrophic cardiomyopathy (HCM), the causative mutations are predominantly in genes encoding sarcomeric proteins. The most common genetic mutation causing HCM involves:
- A Dystrophin gene (DMD) on X chromosome
- B Beta-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3) genes ✓
- C Lamin A/C (LMNA) gene encoding nuclear envelope proteins
- D Desmin (DES) gene encoding intermediate filaments linking sarcomeres
Explanation
HCM is the most common inherited cardiac disorder (1:500), caused by autosomal dominant mutations in sarcomeric protein genes. MYH7 (encoding beta-myosin heavy chain) and MYBPC3 (encoding myosin-binding protein C) together account for approximately 70–80% of identified HCM mutations. MYH7 mutations tend to cause earlier-onset disease with higher penetrance; MYBPC3 mutations cause later-onset, more variable penetrance. These mutations generally cause a hypercontractile state through altered cross-bridge cycling kinetics. Dystrophin mutations cause X-linked dilated cardiomyopathy; LMNA mutations cause dilated cardiomyopathy with conduction disease; desmin mutations cause myofibrillar cardiomyopathy.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.