Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy
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RESEARCH ARTICLE
Open Access
Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy Lazar Velicki1,2*† , Djordje G. Jakovljevic3,9*†, Andrej Preveden1,2, Miodrag Golubovic1,2, Marija Bjelobrk1,2, Aleksandra Ilic1,2, Snezana Stojsic1,2, Fausto Barlocco4, Maria Tafelmeier5, Nduka Okwose3, Milorad Tesic6, Paul Brennan3, Dejana Popovic6, Arsen Ristic6, Guy A. MacGowan3, Nenad Filipovic7,8, Lars S. Maier5† and Iacopo Olivotto4† Abstract Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations. Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography. Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e′ ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079). Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3. Keywords: Hypertrophic cardiomyopathy, HCM, Hereditary cardiac disease, Left ventricular hypertrophy, MYBPC3, MYH7 *Correspondence: [email protected]; [email protected] † Lars S. Maier and OIacopo Olivotto: Joint last authors † Lazar Velicki and Djordje G. Jakovljevic: Joint first authors 1 Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia 3 Cardiovascular Research, Translational and Clinical Research Institute, Medicine, Newcastle University, Newcastl
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