Abstract
Congenital heart disease is the most common birth defect, affecting 0.7% of liveborn infants [1]. There is overwhelming evidence supporting a genetic etiology for most congenital heart defects in humans [2]. This inc1udes familial occurrences and a high recurrence rate, an association with specific chromosomal disorders, and the high occurrence rate of congenital defects in dysmorphic syndromes. To date, there is a limited number of genes that has been demonstrated to cause congenital heart defects in humans. That number is bound to increase rapidly with the completion of the human genome sequencing project. In this review, congenital heart defects are defined as those defects that are present and can be diagnosed at birth. Other structural heart defects in which specific genes have been identified, including cardiomyopathies, long QT syndrome and Marfan syndrome, are discussed in separate chapters.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Ferencz C., Loffredo C.A., Correa-Villasenor A., Wilson P.D. (eds.) Perspectives in pediatric cardiology, Vol. 5, Genetic and environmental risk factors of major cardiovascular malformations.The Baltimore-Washington Infant Study 1981-1989. Futura: Armonk, NY, 1997.
Grossfeld, P.D.; Rothman A., Gruber P.; Chien K.R. Molecular genetics of congenital heart disease, in “ Molecular Basis of Cardiovascular Disease” (Ed. Chien K.R.) W.B. Saunders 1999; 135–65.
Geisterfer-Lowrance, A.A.; Kass, S.; Tanigawa, G.; Vosberg, H.P.; McKenna, W.; Seidman, C.E.; Seidman, J.G. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell, 1990; 62:999–1006.
Tsipouras, P.; Del Mastro, R.; Sarfarazi, M.; et al and international Marfan syndrome Collaborative Study: Genetic linkage of the Marfan syndrome, ectopia lentis, and congenital contractural arachnodactyly to the fibrillin genes on chromosomes 15 and 5. N Engl J Med 1992; 326: 905–90.
Morris, C.A.; Loker, J.; Ensing, G.; Stock, A.D. Supravalvular aortic stenosis cosegregates with a familial6; 7 translocation which disrupts the elastin gene. Am J Med Genet 1993; 4:737–44.
Chen, J.; Kubalak, S.W.; Chien, K.R. Ventricular muscle-restricted targeting of the RXR alpha gene reveals a non-cell-autonomous requirement in cardiac chamber morphogenesis. Developrnent 1998; 125:1943–49.
Li, Q.Y.; Newbury-Ecob, R.A.; Terrett, J.A.; Wilson, D.I.; Curtis, A.R.; Vi, C.H.; Gebuhr, T.; Bullen, P.J.; Robson, S.C.; Strachan, T.; Bonnet, D.; Lyonnet, S.; Young, I.D.; Raebum, J.A.; Buckler, A.J.; Law, D.J.; Brook, J.D. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet 1997; 1:21–9.
Basson, C.T.; Bachinsky, D.R.; Lin, R.C.; Levi, T.; Elkins, J.A; Soults, J.; Grayzel, D.; Kroumpouzou, E.; Traill, T.A.; Leblanc-Straceski, J.; Renault, B.; Kucherlapati, R.; Seidman, J.G.; Seidman, C.E. Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome Nature Genetics, 1997; 1:30–5.
Schott, J.J.; Benson, D.W.; Basson, C.T.; Pease, W.; Silberbach, G.M.; Moak, J.P.; Maron, B.J.; Seidman, C.E.; Seidman, J.G. Congenital heart disease caused by mutations in the transcription factor NKX2-5 Science, 1998: 5373:108–11.
Oda, T.; Elkahloun, A.G.; Pike, B.L.; Okajima, K.; Krantz, I.D.; Genin, A.; Piccoli, D.A.; Meltzer, P.S.; Spinner, N.B.; Collins, F.S.; Chandrasekharappa, S.C.. Mutations in the human Jaggedl gene are responsible for Alagille syndrome. Nat Genet 1997; 3:235–42.
Goldmuntz, E.; Clark, B.J.; Mitchell, L.E.; Jawad, A.F.; Cuned, B.F.; Reed, L.; McDonald-McGinn, D.; Chien, P.; Feuer, J.; Zackai, E.N.; Emanuel, B.S.; Driscoll, D.A. Frequency of 22q11 deletions in patients with conotruncal defects. JACC, 1998; 32:492–8.
Jerome, L.A.; Papaioannou, V.E. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat Genet 2001; 3: 286–91.
Merscher, S.; Funke, B.; Epstein, J.A.; Heyer, J.; Puech, A.; Lu, M.M.; Xavier, R.J.; Demay, M.B.; Russell, R.G.; Factor, S.; Tokooya, K.; Jore, B.S.; Lopez, M.; Pandita, R.K.; Lia, M.; Carrion, D.; Xu, H.; Schorle, H.; Kobler, J.B.; Scambler, P.; Wynshaw-Boris, A.; Skoultchi, AI; Morrow, BE; Kucherlapati, R. TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell2001; 104:619–29.
Lindsay, E.A.; Vitelli, F.; Su, H.; Morishima, M.; Huynh, T.; Pramparo, T.; Jurecic, V.; Ogunrinu, G.; Sutherland, H.F.; Scambler, P.J.; Bradley, A.; Baldini, A. TBX1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature, 2001; 410:97–101.
Guris, D.L.; Fantes, J.; Tara, D.; Druker, B.J.; Imamoto, A. Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome. Nat Genet 2001; 3: 293–8.
Satoda, M.; Zhao, F.: Diaz, G.A.; Burn, J.; Goodship, J.; Davidson, R.; Pierpoint, M.E.M.; Gelb, B.D.; Mutations in TF AP2B cause Char syndrome, a familial form of patent ductus arteriosus. Nat Genet 2000; 25:42–6.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Grossfeld, P. (2001). Genetics of Congenital Heart Disease. In: Doevendans, P.A., Wilde, A.A.M. (eds) Cardiovascular Genetics for Clinicians. Developments in Cardiovascular Medicine, vol 239. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-1019-1_3
Download citation
DOI: https://doi.org/10.1007/978-94-010-1019-1_3
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-3888-1
Online ISBN: 978-94-010-1019-1
eBook Packages: Springer Book Archive