{Reference Type}: Journal Article
{Title}: Left-Sided Heart Defects and Laterality Disturbance in Hypoplastic Left Heart Syndrome.
{Author}: Yagi H;Lo CW;
{Journal}: J Cardiovasc Dev Dis
{Volume}: 10
{Issue}: 3
{Year}: Feb 2023 24
{Factor}: 4.415
{DOI}: 10.3390/jcdd10030099
{Abstract}: Hypoplastic left heart syndrome (HLHS) is a complex congenital heart disease characterized by hypoplasia of left-sided heart structures. The developmental basis for restriction of defects to the left side of the heart in HLHS remains unexplained. The observed clinical co-occurrence of rare organ situs defects such as biliary atresia, gut malrotation, or heterotaxy with HLHS would suggest possible laterality disturbance. Consistent with this, pathogenic variants in genes regulating left-right patterning have been observed in HLHS patients. Additionally, Ohia HLHS mutant mice show splenic defects, a phenotype associated with heterotaxy, and HLHS in Ohia mice arises in part from mutation in Sap130, a component of the Sin3A chromatin complex known to regulate Lefty1 and Snai1, genes essential for left-right patterning. Together, these findings point to laterality disturbance mediating the left-sided heart defects associated with HLHS. As laterality disturbance is also observed for other CHD, this suggests that heart development integration with left-right patterning may help to establish the left-right asymmetry of the cardiovascular system essential for efficient blood oxygenation.