Abstract
Congenital heart defects (CHDs) affect 2%–3% of newborns and remain challenging clinically. There is an ongoing project to elucidate the causes of CHDs, focusing primarily on genetics as dictated by the epidemiology. In a paper published in this issue, Santos and colleagues describe studies of Cornelia de Lange syndrome-associated secundum atrial septal defects (ASDs) caused by NIPBL mutations, undertaken with a targeted trapping allele in mice. They show that Nipbl haploinsufficiency in either of two cell populations was sufficient to engender ASDs but that expression solely in either one of those populations was sufficient to rescue them. This work provides novel insights into incomplete penetrance and oligogenic effects underlying CHDs.
Highlights
Congenital heart defects (CHDs) affect 2%–3% of newborns and remain challenging clinically
Of the remaining unexplained 70% of CHD cases? As CHDs are viewed principally as a complex genetic trait, a leading consideration to account for a substantial proportion of the unknown is that several mutations altering various genes relevant for cardiogenesis combine to result in CHDs
In the fascinating research study described in this issue of PLOS Biology, Rosaysela Santos and her colleagues took a novel approach to understanding CHDs observed in a single-gene trait, Cornelia de Lange syndrome (CdLS), using a sophisticated conditional allele in mice [8]
Summary
Congenital heart defects (CHDs) affect 2%–3% of newborns and remain challenging clinically. As CHDs are viewed principally as a complex genetic trait (or an extended series of such traits, ), a leading consideration to account for a substantial proportion of the unknown is that several mutations altering various genes relevant for cardiogenesis combine to result in CHDs. Such an oligogenic model is theoretically sound but practically difficult to validate experimentally.
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