Genetics Of Cardiomyopathy Research Articles

Correction: New Insights into the Genetics of Cardiomyopathies

Correction: New Insights into the Genetics of Cardiomyopathies

Age and Sex Differences in the Genetics of Cardiomyopathy

Cardiomyopathy has variable penetrance. We analyzed age and sex-related genetic differences in 1,397 cardiomyopathy patients (Ontario, UK) with whole genome sequencing. Pediatric cases (n = 471) harbored more deleterious protein-coding variants in Tier 1 cardiomyopathy genes compared to adults (n = 926) (34.6% vs 25.9% respectively, p = 0.0015), with variant enrichment in constrained coding regions. Pediatric patients had a higher burden of sarcomere and lower burden of channelopathy gene variants compared to adults. Specifically, pediatric patients had more MYH7 and MYL3 variants in hypertrophic cardiomyopathy, and fewer TTN truncating variants in dilated cardiomyopathy. MYH7 variants clustered in the myosin head and neck domains in children. OBSCN was a top mutated gene in adults, enriched for protein-truncating variants. In dilated cardiomyopathy, female patients had a higher burden of z-disc gene variants compared to males. Genetic differences may explain age and sex-related variability in cardiomyopathy penetrance. Genotype-guided predictions of age of onset can inform pre-test genetic counseling.Graphical Pediatric cardiomyopathy patients were more likely to be genotype-positive than adults with a higher burden of variants in MYH7, MYL3, TNNT2, VCL. Adults had a higher burden of OBSCN and TTN variants. Females with dilated cardiomyopathy (DCM) had a higher burden of z-disc gene variants compared to males.

Editorial introductions.

Current Opinion in Cardiology was launched in 1985. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of cardiology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Ali J. MarianAli J. MarianDr Ali J. Marian joined the faculty at the Department of Medicine (Cardiology) at Baylor College of Medicine, USA, in 1992 and was recruited to The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth, USA, in 2006. His colleagues nationally and internationally recognize him for his research achievements and expertise in genetics of cardiomyopathies. He received the Young Investigator Award from the American College of Cardiology, the Junior Faculty Award for research from the American Federation of Medical Research, the Award for Excellence in Research at Baylor College of Medicine, the Established Investigator Award by the American Heart Association, the Clinician-Scientist Award in Translational Research from Burroughs Wellcome Fund and the Best Editor Award from the American Heart Association. Dr Marian is an Associate Editor of Cardiovascular Research and Section Editor on Genetics for Current Opinion in Cardiology and Current Atherosclerosis Reports. He was a Deputy Editor of Circulation Research, Associate Editor for Circulation and an Associate Editor for European Journal of Clinical Investigation. He received the Best Editor Award from the American Heart Association for his work for Circulation Research. Dr Marian has co-authored ∼ 200 manuscripts in peer-reviewed journals. He has served as a reviewer for > 100 National Institute of Health, American Heart Association and other organizations study sections. Dr Marian's research is supported by grants from NHLBI-NIH, Leducq Foundation Trans-Atlantic Network of Excellence and local foundations. Rebecca CogswellRebecca CogswellDr Cogswell completed internal medicine residency, chief residency, and cardiology fellowship at the University of California, San Francisco, USA. While at UCSF, she also completed a year of advanced clinical research training. She then went on to complete Advanced Heart Failure fellowship at the University of Minnesota, USA. She has been on faculty at the University of Minnesota since 2013 and is presently the Medical Director of Mechanical Circulatory Support Program. Dr Cogswell's research focus is the skeletal muscle changes that occur in end stage heart failure. Specifically, she is interested in what these changes can reveal about optimal timing of advanced heart failure therapies and using these measures to predict outcomes after mechanical circulatory support. She has built a left ventricular assist device database at the University of Minnesota and is collaborating with other centers towards answering several clinical questions in the contemporary continuous flow LVAD population. She is presently the Advanced Heart Failure fellowship director and is an active reviewer for Journal of Heart Lung Transplant and Circulation Heart Failure. She is a principle investigator for several heart failure and LVAD related clinical trials. In 2017, she was appointed to the Medtronic Heart Failure Advisory Board. In addition, she developed and directs to the Infiltrative Cardiomyopathies Clinic at the University of Minnesota. Gene KimGene KimDr Kim is a cardiologist with the Advanced heart failure, Cardiac transplant, and Mechanical Circulatory Support Program at the University of Chicago Medicine, USA. He is an Assistant Professor of Medicine and the Advanced Heart Failure Fellowship Program Director. His medical school, residency, and fellowship training were completed at the University of Chicago. Dr Kim's research interests include the genetic and epigenetic regulation of heart failure and arrhythmogenesis with publications on the role of microRNAs in cardiomyopathy. His interests also include myocardial recovery, extracellular matrix in failing myocardium, and the role of inflammation and angiogenesis in LVAD patients. He has published over 80 articles and book chapters and is an investigator in numerous clinical trials.

Minor hypertrophic cardiomyopathy genes, major insights into the genetics of cardiomyopathies.

Hypertrophic cardiomyopathy (HCM) was traditionally described as an autosomal dominant Mendelian disease but is now increasingly recognized as having a complex genetic aetiology. Although eight core genes encoding sarcomeric proteins account for >90% of the pathogenic variants in patients with HCM, variants in several additional genes (ACTN2, ALPK3, CSRP3, FHOD3, FLNC, JPH2, KLHL24, PLN and TRIM63), encoding non-sarcomeric proteins with diverse functions, have been shown to be disease-causing in a small number of patients. Genome-wide association studies (GWAS) have identified numerous loci in cardiomyopathy case-control studies and biobank investigations of left ventricular functional traits. Genes associated with Mendelian cardiomyopathy are enriched in the putative causal gene lists at these loci. Intriguingly, many loci are associated with both HCM and dilated cardiomyopathy but with opposite directions of effect on left ventricular traits, highlighting a genetic basis underlying the contrasting pathophysiological effects observed in each condition. This overlap extends to rare Mendelian variants with distinct variant classes in several genes associated with HCM and dilated cardiomyopathy. In this Review, we appraise the complex contribution of the non-sarcomeric, HCM-associated genes to cardiomyopathies across a range of variant classes (from common non-coding variants of individually low effect size to complete gene knockouts), which provides insights into the genetic basis of cardiomyopathies, causal genes at GWAS loci and the application of clinical genetic testing.

New insights into the genetics of cardiomyopathies.

Common genetic variants, modifiable risk factors and a polygenic risk score all have important implications for disease susceptibility, severity and variability in hypertrophic cardiomyopathy.

Genetics of Cardiomyopathy: Clinical and Mechanistic Implications for Heart Failure

Genetics has played an important role in the understanding of different cardiomyopathies, and the field of heart failure (HF) genetics is progressing rapidly. Much research has also focused on distinguishing markers of risk in patients with cardiomyopathy using genetic testing. While these efforts currently remain incomplete, new genomic technologies and analytical strategies provide promising opportunities to further explore the genetic architecture of cardiomyopathies, afford insight into the early manifestations of cardiomyopathy, and help define the molecular pathophysiological basis for cardiac remodeling. Cardiovascular physicians should be fully aware of the utility and potential pitfalls of incorporating genetic test results into pre-emptive treatment strategies for patients in the preliminary stages of HF. Future work will need to be directed towards elucidating the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype-phenotype relationship. This future research should aim to further our ability to identify, diagnose, and treat disorders that cause HF and sudden cardiac death in young patients, as well as prioritize improving our ability to stratify the risk for these patients prior to the onset of the more severe consequences of their disease.

Categorized Genetic Analysis in Childhood-Onset Cardiomyopathy.

Childhood-onset cardiomyopathy is a heterogeneous group of conditions the cause of which is largely unknown. The influence of consanguinity on the genetics of cardiomyopathy has not been addressed at a large scale. To unravel the genetic cause of childhood-onset cardiomyopathy in a consanguineous population, a categorized approach was adopted. Cases with childhood-onset cardiomyopathy were consecutively recruited. Based on the likelihood of founder mutation and on the clinical diagnosis, genetic test was categorized to either (1) targeted genetic test with targeted mutation test, single-gene test, or multigene panel for Noonan syndrome, or (2) untargeted genetic test with whole-exome sequencing or whole-genome sequencing. Several bioinformatics tools were used to filter the variants. Two-hundred five unrelated probands with various forms of cardiomyopathy were evaluated. The median age of presentation was 10 months. In 30.2% (n=62), targeted genetic test had a yield of 82.7% compared with 33.6% for whole-exome sequencing/whole-genome sequencing (n=143) giving an overall yield of 53.7%. Strikingly, 96.4% of the variants were homozygous, 9% of which were found in 4 dominant genes. Homozygous variants were also detected in 7 novel candidates (ACACB, AASDH, CASZ1, FLII, RHBDF1, RPL3L, ULK1). Our work demonstrates the impact of consanguinity on the genetics of childhood-onset cardiomyopathy, the value of adopting a categorized population-sensitive genetic approach, and the opportunity of uncovering novel genes. Our data suggest that if a founder mutation is not suspected, adopting whole-exome sequencing/whole-genome sequencing as a first-line test should be considered.

Editorial introductions

Current Opinion in Cardiology was launched in 1985. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of cardiology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Ali J. MarianAli J. MarianDr Ali J. Marian joined the faculty at the Department of Medicine (Cardiology) at Baylor College of Medicine, USA, in 1992 and was recruited to The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth, USA, in 2006. His colleagues nationally and internationally recognize him for his research achievements and expertise in genetics of cardiomyopathies. He received the Young Investigator Award from the American College of Cardiology, the Junior Faculty Award for research from the American Federation of Medical Research, the Award for Excellence in Research at Baylor College of Medicine, the Established Investigator Award by the American Heart Association, the Clinician-Scientist Award in Translational Research from Burroughs Wellcome Fund and the Best Editor Award from the American Heart Association. Dr Marian is an Associate Editor of Cardiovascular Research and Section Editor on Genetics for Current Opinion in Cardiology and Current Atherosclerosis Reports. He was a Deputy Editor of Circulation Research, Associate Editor for Circulation and an Associate Editor for European Journal of Clinical Investigation. He received the Best Editor Award from the American Heart Association for his work for Circulation Research. Dr Marian has co-authored ∼ 200 manuscripts in peer-reviewed journals. He has served as a reviewer for > 100 National Institute of Health, American Heart Association and other organizations study sections. Dr Marian's research is supported by grants from NHLBI-NIH, Leducq Foundation Trans-Atlantic Network of Excellence and local foundations Rebecca CogswellRebecca CogswellDr Cogswell completed internal medicine residency, chief residency, and cardiology fellowship at the University of California, San Francisco, USA. While at UCSF, she also completed a year of advanced clinical research training. She then went on to complete Advanced Heart Failure fellowship at the University of Minnesota, USA. She has been on faculty at the University of Minnesota since 2013 and is presently the Medical Director of Mechanical Circulatory Support Program. Dr Cogswell's research focus is the skeletal muscle changes that occur in end stage heart failure. Specifically, she is interested in what these changes can reveal about optimal timing of advanced heart failure therapies and using these measures to predict outcomes after mechanical circulatory support. She has built a left ventricular assist device database at the University of Minnesota and is collaborating with other centers towards answering several clinical questions in the contemporary continuous flow LVAD population. She is presently the Advanced Heart Failure fellowship director and is an active reviewer for Journal of Heart Lung Transplant and Circulation Heart Failure. She is a principle investigator for several heart failure and LVAD related clinical trials. In 2017, she was appointed to the Medtronic Heart Failure Advisory Board. In addition, she developed and directs to the Infiltrative Cardiomyopathies Clinic at the University of Minnesota. Gene KimGene KimDr Kim is a cardiologist with the Advanced heart failure, Cardiac transplant, and Mechanical Circulatory Support Program at the University of Chicago Medicine, USA. He is an Assistant Professor of Medicine and the Advanced Heart Failure Fellowship Program Director. His medical school, residency, and fellowship training were completed at the University of Chicago. Dr Kim's research interests include the genetic and epigenetic regulation of heart failure and arrhythmogenesis with publications on the role of microRNAs in cardiomyopathy. His interests also include myocardial recovery, extracellular matrix in failing myocardium, and the role of inflammation and angiogenesis in LVAD patients. He has published over 80 articles and book chapters and is an investigator in numerous clinical trials.

Genetics of inherited cardiomyopathies in Africa.

In sub-Saharan Africa (SSA), the burden of noncommunicable diseases (NCDs) is rising disproportionately in comparison to the rest of the world, affecting urban, semi-urban and rural dwellers alike. NCDs are predicted to surpass infections like human immunodeficiency virus, tuberculosis and malaria as the leading cause of mortality in SSA over the next decade. Heart failure (HF) is the dominant form of cardiovascular disease (CVD), and a leading cause of NCD in SSA. The main causes of HF in SSA are hypertension, cardiomyopathies, rheumatic heart disease, pericardial disease, and to a lesser extent, coronary heart disease. Of these, the cardiomyopathies deserve greater attention because of the relatively poor understanding of mechanisms of disease, poor outcomes and the disproportionate impact they have on young, economically active individuals. Morphofunctionally, cardiomyopathies are classified as dilated, hypertrophic, restrictive and arrhythmogenic; regardless of classification, at least half of these are inherited forms of CVD. In this review, we summarise all studies that have investigated the incidence of cardiomyopathy across Africa, with a focus on the inherited cardiomyopathies. We also review data on the molecular genetic underpinnings of cardiomyopathy in Africa, where there is a striking lack of studies reporting on the genetics of cardiomyopathy. We highlight the impact that genetic testing, through candidate gene screening, association studies and next generation sequencing technologies such as whole exome sequencing and targeted resequencing has had on the understanding of cardiomyopathy in Africa. Finally, we emphasise the need for future studies to fill large gaps in our knowledge in relation to the genetics of inherited cardiomyopathies in Africa.

Editorial introductions

Current Opinion in Cardiology was launched in 1985. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of cardiology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Ali J. MarianAli J. MarianDr Ali J. Marian joined the faculty at the Department of Medicine (Cardiology) at Baylor College of Medicine, USA, in 1992 and was recruited to The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth, USA, in 2006. His colleagues nationally and internationally recognize him for his research achievements and expertise in genetics of cardiomyopathies. He received the Young Investigator Award from the American College of Cardiology, the Junior Faculty Award for research from the American Federation of Medical Research, the Award for Excellence in Research at Baylor College of Medicine, the Established Investigator Award by the American Heart Association, the Clinician-Scientist Award in Translational Research from Burroughs Wellcome Fund and the Best Editor Award from the American Heart Association. Dr Marian is a Deputy Editor for Circulation Research. He is an Associate Editor for European Journal of Clinical Investigation, Section Editor on Genetics for Current Opinion in Cardiology and Current Atherosclerosis Reports and a former Associate Editor for Circulation. Dr Marian has co-authored over 180 manuscripts in peer-reviewed journals. He has served as a reviewer for > 100 National Institute of Health, American Heart Association and other organization's study sections. Dr Marian's research is supported by grants from NHLBI-NIH, Leducq Foundation Trans-Atlantic Network of Excellence and local foundations. Rebecca CogswellRebecca CogswellDr Cogswell completed internal medicine residency, chief residency, and cardiology fellowship at the University of California, San Francisco, USA. While at UCSF, she also completed a year of advanced clinical research training. She then went on to complete Advanced Heart Failure fellowship at the University of Minnesota, USA. She has been on faculty at the University of Minnesota since 2013 and is presently the Medical Director of Mechanical Circulatory Support Program. Dr Cogswell's research focus is the skeletal muscle changes that occur in end stage heart failure. Specifically, she is interested in what these changes can reveal about optimal timing of advanced heart failure therapies and using these measures to predict outcomes after mechanical circulatory support. She has built a left ventricular assist device database at the University of Minnesota and is collaborating with other centers towards answering several clinical questions in the contemporary continuous flow LVAD population. She is presently the Advanced Heart Failure fellowship director and is an active reviewer for Journal of Heart Lung Transplant and Circulation Heart Failure. She is a principle investigator for several heart failure and LVAD related clinical trials. In 2017, she was appointed to the Medtronic Heart Failure Advisory Board. In addition, she developed and directs to the Infiltrative Cardiomyopathies Clinic at the University of Minnesota. Gene KimGene KimDr Kim is a cardiologist with the Advanced heart failure, Cardiac transplant, and Mechanical Circulatory Support Program at the University of Chicago Medicine, USA. He is an Assistant Professor of Medicine and the Advanced Heart Failure Fellowship Program Director. His medical school, residency, and fellowship training were completed at the University of Chicago. Dr Kim's research interests include the genetic and epigenetic regulation of heart failure and arrhythmogenesis with publications on the role of microRNAs in cardiomyopathy. His interests also include myocardial recovery, extracellular matrix in failing myocardium, and the role of inflammation and angiogenesis in LVAD patients. He has published over 80 articles and book chapters and is an investigator in numerous clinical trials.

Genetics of cardiomyopathies: novel perspectives with next generation sequencing.

Cardiomyopathies are a heterogeneous group of primary diseases of the myocardium usually of genetic origin and with familial presentation. The identification of multiple genetic causes for these diseases has opened a new window for early diagnosis, understanding of their natural history and improvement in risk stratification and management. However, in the past years, the clinical application of genetics has been limited by the prohibiting cost and restricted yield of the available genotyping technologies. The emergence of Next Generation Sequencing (NGS) has completely changed this scenario. This group of sequencing technologies allow the evaluation of hundreds or even thousands of genes in parallel at an affordable cost. Now the challenge is not genotyping per se but the interpretation of the complex results that NGS generates. In this paper we review the main aspects related to the application and impact of Next Generation Sequencing in the study of cardiomyopathies: technology, analysis procedures, bioinformatics, clinical validation and interpretation of results.

Recent Developments in the Genetics of Cardiomyopathies

The complex nature of familial cardiomyopathies is incompletely understood. The effective management of patients and their relatives therefore requires a multidisciplinary approach involving a specialist genetic counselling service. Genetic testing is clinically available, and our knowledge in this area continues to grow with developments in new technologies. Many of the genes associated are not specific to a particular type of cardiomyopathy, and recent data suggests that some patients may have more than one mutation or variant contributing to disease. Developments in next generation sequencing have enabled us to accurately and efficiently sequence these areas of interest, but the current capacity to analyse and interpret this data (bioinformatics) remains a major limitation. Genetic guided therapies have the potential to revolutionise our management of affected patients in the future but this is far from being a clinical reality at the current time.

Uptake of Cardiac Screening and Genetic Testing Among Hypertrophic and Dilated Cardiomyopathy Families

Cardiomyopathy is a genetically and clinically heterogeneous, life threatening disease which affects people of all ages. Recent guidelines provide recommendations for cardiac screening and genetic testing in at-risk relatives, but the uptake and impact of these measures in the United States is unknown. This is a single institution retrospective study that characterizes the uptake of cardiac screening and genetic testing for relatives of a cohort of 57 probands with hypertrophic (HCM) and dilated cardiomyopathy (DCM) who underwent both clinical evaluation and genetic testing. Cardiac screening was indicated for 302 relatives. One hundred and seventy-three (57%) completed cardiac screening. Forty of the 57 probands were mutation positive and genetic testing was indicated for 213 relatives. Eighty-four (39%) completed genetic testing. The uptake of cardiac surveillance was greater than the uptake of genetic testing (p < 0.0001) among relatives of mutation positive probands. Within the group of at-risk, asymptomatic relatives of probands, cardiac screening and genetic testing were positive in 25% and 40% of cases, respectively. These data demonstrate the important role and utility of cascade cardiac screening and genetic testing in the care of patients and families with HCM or DCM. The approach to cardiac screening and genetic testing should be family-specific and requires expertise in the genetics of cardiomyopathy.

Genetics of Cardiomyopathies in Children

Cardiomyopathies are diseases of the heart muscle leading to heart failure and/or an increased risk of arrhythmogenic sudden cardiac death. These disorders represent a major cause of morbidity and mortality in children. In childhood forms of cardiomyopathy, genetic etiologies are frequent, but non-genetic or acquired causes, such viral infection, also play a significant role. In the last twenty years, the genetic causes of cardiomyopathies have been increasingly identified and clinical correlations are beginning to be defined. Here we present an overview of the recent advances in our understanding of the genetics of cardiomyopathies in children and what is known about the pathophysiological mechanisms underlying these gene-related forms of disease.

Recent progress in the genetics of cardiomyopathy and its role in the clinical evaluation of patients with cardiomyopathy

This review will provide an overview of the genetic basis of cardiomyopathy with an emphasis on the clinically relevant breakthroughs that have occurred recently and their role in the evaluation of patients with cardiomyopathy. Recent developments that have occurred in genetic cardiomyopathy include the finding of a shared genetic basis of familial dilated cardiomyopathy in at least a subset of cases of peripartum cardiomyopathy; the increased yield for the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) when genetic testing is incorporated into Task Force Criteria; and the value of testing a spectrum of implicated genes in hypertrophic cardiomyopathy and ARVC because of the severe phenotype associated with compound mutations. Recent progress in genetic cardiomyopathy points to the potential value of genetic testing in shaping the clinician's ability to diagnose and understand the pathogenetic basis of the inherited cardiomyopathies. The rapid rate at which the field is progressing emphasizes the importance of referral of such patients to multidisciplinary teams equipped to address the complex biological, social and psychological issues that accompany the genetic diagnosis of inherited cardiomyopathy.

Molecular biology of heart disease

Dr. Robert Roberts is currently Professor of Medicine and Director of the Ruddy Canadian Cardiovascular Genetics Centre along with being President and CEO of the University of Ottawa Heart Institute. Prior to this appointment, he was Chief of Cardiology for 23 years at Baylor College of Medicine, Houston, Texas. His original research was in cardiac enzymology which led to the development of the MBCK test which was the standard diagnostic assay for myocardial infarction for more than 3 decades. In the late 1970s, his research interests switched to molecular biology and the genetics of cardiomyopathies. He is regarded as one of the founders of molecular cardiology and has identified and sequenced more than 20 genes responsible for cardiovascular disorders. In the past 6 years, he has pursued genome-wide association studies to identify genes predisposing to coronary artery disease (CAD) and myocardial infarction. The first genetic variant for CAD, 9p21, was identified by Dr. Robert's laboratory and, in collaboration with the international consortium, CARDIoGRAM, has identified 13 novel genes for CAD.

Genetika kardiomyopatií

Genetika kardiomyopatií

The genetics of cardiomyopathy: Genotyping and genetic counseling

Three decades of ongoing research into the identification of genes responsible for both cardiomyopathies and ion channel diseases has facilitated a progressive understanding of the pathophysiology of inherited arrhythmogenic diseases. Recent discoveries in the area of genetics promise to significantly change the current clinical practice of cardiology, as rapid advances in technology and a coincident reduction of costs associated with sequencing have pushed the "translation" of genomic information from bench to bedside. In turn, clinicians have at their disposal new tools for more accurate diagnosis of diseases, as well as for better calculation of health risks for affected families. It is clear, however, that the integration of genetic analysis into frontline clinical cardiology has not yet occurred, especially for heritable cardiomyopathic processes; no one simplified method exists for diagnosing these complex cardiac disease states. It therefore is important to assess the present and future roles of genetic analysis and counseling in clinical practice and how to assist the transition of genetic screening into current care to ensure the appropriate practical use of genetic tests in the routine clinical setting. The purpose of this discussion is to provide a concise review of recent developments in the field of heritable cardiomyopathies, with specific regard to genetic testing and genetic counseling.

Dissecting the genetics of cardiomyopathy in India: A tale of ten steps

Dissecting the genetics of cardiomyopathy in India: A tale of ten steps

The genetics of cardiomyopathies: What clinicians should know

Primary myocardial diseases, or cardiomyopathies, affect millions of individuals worldwide. Although there are sizable environmental contributors to the etiology of these diseases, many cardiomyopathies have a high degree of heritability and, thus, genetic aspects of diagnosis and therapy warrant special consideration. The past two decades have seen enormous progress in elucidating the epidemiology, genetic architecture, and pathophysiology of these diseases. In this review, we focus on translating advances in the genetics of cardiomyopathies to clinical care. We discuss the underlying genetic and phenotypic complexity of these disorders, highlighting the implications for diagnosis, treatment, screening, and prognosis of patients and their family members.