Genetics in the understanding of the hypoplastic left heart syndrome

Abstract

Research methods of the complex genetic heterogeneity of the hypoplastic left heart syndrome (HLHS) are presented using as the example. The common genetic basis of the left ventricular outfl ow tract (LVOT) defects, where HLHS is accompanied by bicuspid aortic valve (BAV), aortic valve stenosis (AVS), coarctation of the aorta (Coa), dilatation of the ascending aorta (AOD), and the Shone syndrome, is also investigated. The literature presents evidence for mutual connection of these defects with a common etiopathogenic source through epidemiological knowledge, analysis of the occurrence of the mentioned defects within families or smaller groups, and through family trees. Current methods of evaluating polygenic infl uences according to logarithm of odds (LOD) marker with a level of signifi cance marked as suspect or signifi cant are presented. Hypoplastic left heart syndrome is linked with chromosomal regions 10q22 and 6q23 with maximum LOD 3.1 and 3.2 (p<0.001). In HLHS and BAV groups of patients, locus 14q23 revealed an extremely high degree of linkage (LOD 4.1) of these two defects. The latest studies by Hinton et al. (2008, 2009), MacBridge (2009, 2010), and Garge et al. (2011) are presented by describing the methods, through tables and multilayer LOD markers, through images (family tree, NOTCH1 missense mutations), and corresponding discussion. Finally, the author presents his own experiences from BAV study and the connection of this lesion with other LVOT defects in 100 patients in a retrospective study ten-years.