Genetic cardiomyopathies causing heart failure.

نویسندگان

Thomas J Cahill

Houman Ashrafian

Hugh Watkins

چکیده

Despite the striking advances in medical and surgical therapy, the morbidity, mortality, and economic burden of heart failure (HF) remain unacceptably high. There is increasing evidence that the risk and course of HF depend on genetic predisposition; however, the genetic contribution to HF is heterogeneous and complex. At one end of the spectrum are the familial monogenic HF syndromes in which causative mutations are rare but highly penetrant. At the other, HF susceptibility and course may be influenced by more common, less penetrant genetic variants. As detailed in this review, efforts to unravel the basis of the familial cardiomyopathies at the mendelian end of the spectrum already have begun to deliver on the promise of informative mechanisms, novel gene-based diagnostics, and therapies for distinct subtypes of HF. However, continued progress requires the differentiation of pathogenic mutations, disease modifiers, and rare, benign variants in the deluge of data emerging from increasingly accessible novel sequencing technologies. This represents a significant challenge and demands a sustained effort in analysis of extended family pedigrees, diligent clinical phenotyping, and systematic annotation of human genetic variation.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Advances in Heart Failure Progress With Genetic Cardiomyopathies Screening, Counseling, and Testing in Dilated, Hypertrophic, and Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

This review focuses on the genetic cardiomyopathies: principally dilated cardiomyopathy, with salient features of hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia/cardiomyopathy, regarding genetic etiology, genetic testing, and genetic counseling. Enormous progress has recently been made in identifying genetic causes for each cardiomyopathy, and key phenotype and genot...

متن کامل

Progress with genetic cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular dysplasia/cardiomyopathy.

متن کامل

The Mutations Associated with Dilated Cardiomyopathy

Cardiomyopathy is an important cause of heart failure and a major indication for heart transplantation in children and adults. This paper describes the state of the genetic knowledge of dilated cardiomyopathy (DCM). The identification of the causing mutation is important since presymptomatic interventions of DCM have proven value in preventing morbidity and mortality. Additionally, as in genera...

متن کامل

Genetics of inherited cardiomyopathy.

During the past two decades, numerous disease-causing genes for different cardiomyopathies have been identified. These discoveries have led to better understanding of disease pathogenesis and initial steps in the application of mutation analysis in the evaluation of affected individuals and their family members. As knowledge of the genetic abnormalities, and insight into cellular and organ biol...

متن کامل