title: Genetic testing in the management of relatives of patients with hypertrophic cardiomyopathy.
abstract: Hypertrophic cardiomyopathy is the most common genetic cardiac disease with vast genetic heterogeneity. First-degree relatives of patients with HCM are at 50% risk of inheriting the disease-causing mutation. Genetic testing is helpful in identifying the relatives harbouring the mutations. When genetic testing is not available, relatives need to be examined regularly. We tested a cohort of 99 unrelated patients with HCM for mutations in MYH7, MYBPC3, TNNI3 and TNNT2 genes. In families with identified pathogenic mutation, we performed genetic and clinical examination in relatives to study the influence of genetic testing on the management of the relatives and to study the usefulness of echocardiographic criteria for distinguishing relatives with positive and negative genotype. We identified 38 genetic variants in 47 patients (47 %). Fifteen of these variants in 21 patients (21 %) were pathogenic mutations. We performed genetic testing in 52 relatives (18 of them (35 %) yielding positive results). Genetic testing of one HCM patient allowed us to omit 2.45-5.15 future cardiologic examinations of the relatives. None of the studied echocardiographic criteria were significantly different between the relatives with positive and negative genotypes, with the exception of a combined echocardiographic score (genotype positive vs. genotype negative, 3.316 vs. -0.489, P = 0.01). As a conclusion, our study of HCM patients and their relatives confirmed the role of genetic testing in the management of the relatives and found only limited benefit of the proposed echocardiographic parameters in identifying disease-causing mutation carriers.
authors.affiliation: Department of Cardiology, Second Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Tomašov
authors.affiliation: Laboratory for Molecular Genetics and Oncology, Genomac Research Institute, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Minárik
authors.affiliation: Department of Cardiology, Second Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: D
authors.initials: D
authors.lastname: Zemánek
authors.affiliation: Department of Cardiology, Second Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Čadová
authors.affiliation: Department of Cardiology, Second Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: S
authors.initials: S
authors.lastname: Homolová
authors.affiliation: Third Department of Internal Medicine - Department of Cardiology, University Hospital Královské Vinohrady, Prague, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Čurilka
authors.affiliation: Third Department of Internal Medicine - Department of Cardiology, University Hospital Královské Vinohrady, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Pěnička
authors.affiliation: Laboratory for Molecular Genetics and Oncology, Genomac Research Institute, Prague, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Benešová
authors.affiliation: Laboratory for Molecular Genetics and Oncology, Genomac Research Institute, Prague, Czech Republic.
authors.forename: B
authors.initials: B
authors.lastname: Belšánová
authors.affiliation: Third Department of Internal Medicine - Department of Cardiology, University Hospital Královské Vinohrady, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Gregor
authors.affiliation: Department of Cardiology, Second Faculty of Medicine, Charles University in Prague and University.
authors.forename: J
authors.initials: J
authors.lastname: Veselka
mesh_terms: D000293:Adolescent; D000328:Adult; D024722:Cardiac Myosins / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D015331:Cohort Studies; D004452:Echocardiography; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D020107:Troponin T / Q000235:genetics; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D020107:Troponin T; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human; C545568:TNNT2 protein, human; C518660:TNNT3 protein, human