TY - CHAP M1 - Book, Section TI - MENDELIAN BASIS OF CONGENITAL AND OTHER CARDIOVASCULAR DISEASES A1 - Marian, Ali J. A1 - Brugada, Ramon A1 - Roberts, Robert A2 - Fuster, Valentin A2 - Harrington, Robert A. A2 - Narula, Jagat A2 - Eapen, Zubin J. PY - 2017 T2 - Hurst's The Heart, 14e AB - Genetic factors play a significant role in almost all cardiovascular disorders. Genetic defects are responsible for malformations of the heart and blood vessels, which account for the largest number of human birth defects. The estimated incidence of congenital heart disease is approximately 1% of all live births.1 The prevalence is estimated to be 10-fold higher among stillbirths.2 Genetic defects are responsible for familial cardiovascular disorders, such as cardiomyopathies, the long QT syndromes (LQTSs), as well as sporadic forms of such disorders. Over 3600 genes have been identified to date for single-gene disorders with Mendelian patterns of inheritance. Likewise, genetic factors predispose to common complex phenotypes, such as atherosclerosis and hypertension. Over 4000 loci have been mapped for complex phenotypes. Molecular genetic studies provide the opportunity to decipher the genetic basis and pathogenesis of many disorders, especially cardiovascular diseases. Genetic discoveries have the potential to lead to identification of new targets for the prevention and treatment of human diseases. This is best illustrated in the case of the PCSK9 gene, which was genetically mapped in 2003 as a cause of autosomal dominant hypercholesterolemia.3 Recently, the discovery led to subsequent development of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (evolocumab and alirocumab), which are highly effective for treatment of certain forms of hypercholerolemia.4,5 Partial deciphering of the genetic basis of cardiovascular disease has also ushered in routine genetic testing for various diseases, leading to an accurate genetic-based diagnosis and intervention. Given the rapid pace of genetic discoveries, it is expected that genetic diagnosis and genetic-based interventions will become incorporated into standard practice of medicine in the future. Thus, this chapter provides an overview of the genetic principles, and discusses the genetic basis for cardiovascular disorders as well as the medical and ethical implications of genetic findings. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accesscardiology.mhmedical.com/content.aspx?aid=1161732392 ER -