Loss-of-function de novo mutations play an important role in severe human neural tube defects

Neural tube defects (NTDs) are very common and severe birth malformations that are caused by failure of neural tube closure. They are caused by a combination of genetic and environmental factors that remain largely unknown. Anencephaly and spina bifida are severe NTDs that affect reproductive fitness but are still prevalent across generations, suggesting a role for new or de novo mutations (DNMs) in their etiology. We have re-sequenced the exomes of 43 sporadic cases affected with either spina bifida or anencephaly and their unaffected parents and we have indeed demonstrated that loss of function DNMs play an important role in their causation. Our study also strongly implicates SHROOM3 in the pathogenesis of human NTDs. (By Philippe Lemay, http://jmg.bmj.com/content/early/2015/03/24/jmedgenet-2015-103027 )