TY - JOUR
T1 - The genetic basis of pediatric cardiovascular disease
AU - Strauss, A. W.
AU - Johnson, M. C.
N1 - Funding Information:
From the Departments of Pediatrics and Molecular Biology and Pharmacology, Washington University School of Medicine, and the Division of Pediatric Cardiology, St. Louis Children's Hospital, St. Louis, MO. Supported by National Institutes of Health grants no. DK20407 and no. HL52530. Address reprint requests to Arnold W. Strauss, MD, Department of Pediatrics, St. Louis Children's Hospital, One Children's Place, St. Louis, MO 63110. Copyright 9 1996 by W.B. Saunders Company O146-0005/96/2006-0012505. 00/0
PY - 1996
Y1 - 1996
N2 - Congenital heart disease (CHD), cardiomyopathy, and vasculopathies are common causes of mortality and morbidity in pediatrics, including the perinatal period. This article reviews evidence that single gene defects cause many of the pediatric heart diseases. Vasculopathies discussed include Marfan's syndrome, supravalvar aortic stenosis and Williams' syndrome, Alagille's syndrome, and hereditary telangiectasia, the Osler-Weber-Rendu syndrome. Genetic causes of hypertrophic cardiomyopathy caused by sarcomeric protein mutations (β-cardiac myosin heavy chain) and of dilated cardiomyopathy secondary to structural protein deficiencies (dystrophin) are presented. Defects in proteins essential for myocardial energy production such as oxidative phosphorylation proteins and fatty acid oxidation genes that cause cardiomyopathy or sudden death are described. Gene ablation models in mice, such as RXRα and homeobox gene knockouts, which result in cardiac phenotypes resembling human congenital heart disease, are described. Familial types of human CHD which are being investigated for genetic causes by positional cloning methods and known cytogenetic causes of CHD, including the CATCH-22 syndrome and monosomy at 22q11, are presented. General lessons and principles derived from these new and exciting discoveries in human cardiovascular development are surmised.
AB - Congenital heart disease (CHD), cardiomyopathy, and vasculopathies are common causes of mortality and morbidity in pediatrics, including the perinatal period. This article reviews evidence that single gene defects cause many of the pediatric heart diseases. Vasculopathies discussed include Marfan's syndrome, supravalvar aortic stenosis and Williams' syndrome, Alagille's syndrome, and hereditary telangiectasia, the Osler-Weber-Rendu syndrome. Genetic causes of hypertrophic cardiomyopathy caused by sarcomeric protein mutations (β-cardiac myosin heavy chain) and of dilated cardiomyopathy secondary to structural protein deficiencies (dystrophin) are presented. Defects in proteins essential for myocardial energy production such as oxidative phosphorylation proteins and fatty acid oxidation genes that cause cardiomyopathy or sudden death are described. Gene ablation models in mice, such as RXRα and homeobox gene knockouts, which result in cardiac phenotypes resembling human congenital heart disease, are described. Familial types of human CHD which are being investigated for genetic causes by positional cloning methods and known cytogenetic causes of CHD, including the CATCH-22 syndrome and monosomy at 22q11, are presented. General lessons and principles derived from these new and exciting discoveries in human cardiovascular development are surmised.
UR - http://www.scopus.com/inward/record.url?scp=0030427770&partnerID=8YFLogxK
U2 - 10.1016/S0146-0005(96)80069-3
DO - 10.1016/S0146-0005(96)80069-3
M3 - Article
C2 - 9090781
AN - SCOPUS:0030427770
SN - 0146-0005
VL - 20
SP - 564
EP - 576
JO - Seminars in Perinatology
JF - Seminars in Perinatology
IS - 6
ER -