903 NOVEL MALIGNANT MUTATION IN HYPERTROPHIC CARDIOMYOPATHY

Abstract Background Hypertrophic cardiomyopathy (HCM) is a common inherited disease almost invariably caused by mutations in sarcomeric genes. The HCM phenotype clinically heterogeneous with myocyte hypertrophy, disarray, and myocardial fibrosis as histological hallmarks. This condition recognized an important cause of sudden cardiac death (SCD) the youth heart failure (HF) elderly. Current guidelines mandate genetic analysis class I indication HCM. Indeed, advent next generation sequencing medical practice has led to decipher molecular etiology assess risk family members relevant insights into clinical course. Clinical case A 62-year-old man followed-up at another Hospital non-obstructive diagnosis, was referred our for therapy optimization follow-up. Past history included third degree atrioventricular block age 40 treated dual chamber pacemaker (PM) and, 60, atrial flutter high ventricular response complicated cardiogenic shock stroke. Due worsening systolic function sustained tachycardia he upgraded implantable cardioverter defibrillator which delivered appropriate shocks. Echocardiography performed during current hospitalization showed moderate concentric hypertrophy (intraventricular septum 17 mm, mass index 258 g/m2), dilated ventricle reduced ejection fraction (33%) akinesis mid inferior infero-septal walls left apex, stratified thrombotic apposition. Magnetic resonance contraindicated because non-compatible PM. alteration serum proteins free light chain, rule out systemic disease, extensive imaging diagnosis including bone scintigraphy abdominal ultrasonography resulted negative. While waiting marrow aspiration biopsy patient rapidly deteriorated renal failure, ensuing proteinuria until exitus. After pre-test counseling consented test proband. exome revealed presence missense mutation MYH7 gene. new characterized substitution cysteine residue serine 905 codon Cys905Ser results semi-conservative amino acid may impact disulfide bond formation protein. To date no study described this affecting same codon, Cys905Phe reported only one From biological point view, variant lies head region protein where majority variants are grouped statistically associated phenotype. Several studies that occurrence fibrillation (AF) tends be more prevalent patients carrying mutation. Furthermore, AF substantial HF-related mortality, stroke, severe functional disability. Awareness regarding spectrum probably related SCD or HF combined thorough characterization features, help improve genotype correlation. challenge could elucidate better mechanism enabling cardiologists decision-making patients’ care.