Genetic abberations in congenital heart disease CHDs

Abstract: Congenital heart disease (CHD) affects nearly 1 % of the population. CHD is a group of structural
abnormalities of the heart, which include septal defects, valve defects and lesions affecting the outflow tract. t is
a comple! disease, which may be caused by multiple genetic and environmental factors. "e have compared
different studies in human genetics that led to the identification of more than #$ human genes, involved in
isolated CHD (e.g %C& and C'(D) genes* in lateraly defects ) or genetic syndromes (e.g +,-1 gene in
,llagile syndrome, './1 gene in Di -eorge syndrome ), where CHD is part of the phenotype. 0urthermore,
mapping of genomic copy number variants and e!ome se1uencing of CHD patients have led to the identification
of a large number of candidate disease genes. (!periments in animal models, particularly in mice, have been
used to verify human disease genes and to gain further insight into the molecular pathology behind CHD. 'he
picture emerging from these studies suggest that genetic lesions associated with CHD affect a broad range of
cellular signaling components, from ligands and receptors( H2,3 gene, 401gene, 45'CH) gene ), across
downstream effector molecules to transcription factors and cofactors (C'(D) gene, './1gene ,'./# gene,
'0,6). gene), including chromatin modifiers.
Introduction: CHD is a group of structural abnormalities of the heart, which include septal
defects, valve defects and lesions affecting the outflow tract. -enetically, CHD is a very
heterogeneous disease, about ## human disease genes have been identified so far.
n this study, we aim to summari7e current 8nowledge in the molecular genetics of isolated
congenital heart disease (CHD) and genetic syndromes where CHD is part of phenotype.
-enes associated with laterality defects
'he heart is the first organ that brea8 the bilateral symetry of the developing embryo.
45D,9, 9(0':), ,C;2)., -D01, C0C1, C'(D) and %C& genes have all been locali7ed
to the laterality signaling pathway.
nterestingly, a recent study identified mutations in Nephronophthisis*4 (NPHP4), a ciliary
protein and lin8ed them to a variety of cardiac laterality defects such as transposition of the
great arteries ('-,), atrioventricular septal defects (,;3D), double outlet right ventricle
(D52;), de!trocardia and abnormal pulmonary venous return.