A 48-year-old woman is diagnosed with new-onset dilated cardiomyopathy. LVEF is 25%. She is initiated on guideline-directed medical therapy including beta-blocker, ACEi, and spironolactone. At 3 months, a genetic panel is planned. Which gene mutation is most commonly identified in familial dilated cardiomyopathy?
- A MYH7 (beta-myosin heavy chain) gene
- B LMNA (lamin A/C) gene
- C TTN (titin) gene — truncating variants ✓
- D SCN5A (sodium channel) gene
Explanation
TTN (titin) truncating variants (TTNtv) are the most common genetic cause of familial dilated cardiomyopathy, accounting for approximately 20–25% of all familial DCM cases. Titin is the largest protein in the human genome and is crucial for sarcomere structure and elasticity. MYH7 mutations cause hypertrophic cardiomyopathy more commonly. LMNA mutations cause DCM with prominent conduction disease and are associated with high risk of sudden cardiac death — important to identify but less frequent than TTN variants. SCN5A causes arrhythmias and a DCM phenotype in rare cases.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.