NLRP7 in the spectrum of reproductive wastage: rare non-synonymous variants confer genetic susceptibility to recurrent reproductive wastage

Mutations in NLRP7, a gene with a predicted role in inflammation and apoptosis, are responsible for recurrent molar pregnancies. In this study we report NLRP7 mutations in women with sporadic non-recurrent moles and in women with recurrent spontaneous abortions and no moles. We show that some rare NLRP7 variants, present in the general population, are associated with recurrent reproductive wastage and have functional consequences. Furthermore, we show that patients with NLRP7 mutations and rare variants have placental abnormalities that predispose them to gynecological morbidities and perinatal mortalities. Our data highlight the commonality of these different pathologies, moles, spontaneous abortions, stillbirths, believed, so far, to be independent clinical entities and call for closer follow-up of the pregnancies of women with NLRP7 mutations and rare variants. (By Rima Slim, http://jmg.bmj.com/content/early/2011/06/08/jmg.2011.089144.abstract?papetoc )