The Hole and the Whole: Lessons from Manipulation of Nipbl Deficiency.
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.
The Mindich Child Health and Development Institute and the Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Bruce D
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D000818:Animals; D003635:De Lange Syndrome / Q000235:genetics*; D057895:Haploinsufficiency; D006330:Heart Defects, Congenital / Q000235:genetics; D051379:Mice; D009154:Mutation; D011506:Proteins / Q000235:genetics*
D011506:Proteins