NLRP7 or KHDC3l genes and the etiology of molar pregnancies and recurrent miscarriage

Abstract

Womenwith mutation in both alleles of the NLRP7 or C6orf221/KHDC3L genes are predisposed to diploid biparental moles, but it has also been suggested that mutation in these genes can predispose to diploid androgenetic or triploid moles and to other kinds of reproductive wastage. We have investigated the association between molar pregnancy and recurrent miscarriages regarding changes in the NLRP7 and C6orf221/KHDC3L genes. Our study group can be divided into three sub-cohorts: (i) women having had at least one molar pregnancy and at leasttwo non-mole miscarriages, (ii)womenhaving had recurrent androgenetic hydatidiform moles and (iii)womenhaving had one diploid androgenetic hydatidiform mole and a relative having had a hydatidiform mole (familial hydatidiform moles).We observed a statistically non-significant tendency of non-synonymous variants in NLRP7 to be more frequent in women with familial hydatidiform mole and in women with female family members with hydatidiform mole or non-mole miscarriage comparedwithwomenwith no family history of mole or miscarriage.However,we did not find any unequivocal pathogenic mutations (the term 'unequivocal pathogenic mutations' refers to mutations that indubitably have a pathogenic effect on the affected woman) in NLRP7 or C6orf221/KHDC3L in any of the women in the study group. This indicates that recurrent miscarriages plus hydatidiform mole, recurrent androgenetic hydatidiform moles and familial androgenetic hydatidiform moles in general do not have the same monogenetic etiology as familiar diploid biparental moles © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.