Abstract
BackgroundHypertrophic 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.MethodsAs 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.ResultsThe 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).ConclusionsMajor findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.
Highlights
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people
There was no significant difference between patients carrying the Myosinbinding protein C (MYBPC3) and β-Myosin heavy chain (MYH7) mutations regarding age (49.8 ± 14.3 vs. 55.1 ± 13.3 years, p = 0.211) and gender distribution (21% vs. 33% females, p = 0.321)
Since the development of atrial fibrillation was associated with risk factors such as Left atrium (LA) enlargement, left ventricular (LV) wall thickness, and LV outflow tract obstruction, these results suggest that patients with MYH7 mutation present with a more severe clinical phenotype
Summary
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. The two most common mutations involving thick filament are myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) gene mutations, which are responsible for approximately three-quarters of the identified mutations in HCM patients [9, 10]. Aside from these two, a few other less frequent gene mutations (e.g. troponin I type 3 [TNNI3], troponin T type 2 [TNNT2], α-tropomyosin [TPM1], α-actin [ACTC]) are possible causes of HCM as well and are included in the routine HCM genetic testing [11]. With the introduction and implementation of the next-generation sequencing solutions, the identification of nearly 50 gene mutations associated with some form of HCM throughout literature has become possible [12]
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