title: Women heterozygous for NALP7/NLRP7 mutations are at risk for reproductive wastage: report of two novel mutations.
abstract: Familial recurrent hydatidiform moles are a rare recessive condition in which molar tissues have biparental contribution to their genome. One maternal locus responsible for this condition has been mapped to 19q13.4 and the causative gene, NALP7, identified (HUGO-approved nomenclature is now NLRP7). Here we report a first stop codon, c.295G>T (p.Glu99X) and a missense mutation, c.1970A>T (p.Asp657Val) in NLRP7 in two sisters with RHMs. We found these two mutations and a previously reported one, c.2078G>C (p.Arg693Pro) in a homozygous state, in males with normal reproductive outcomes. This suggests that NLRP7 is not required for normal spermatogenesis. The mother of the patients is heterozygous for Glu99X and had one stillbirth and three normal pregnancies. Our data on this new family and on heterozygous women from previously reported families indicate that women heterozygous for NLRP7 mutations are at risk for reproductive wastage without the manifestation of molar phenotype.
authors.affiliation: Departments of Human Genetics and Obstetrics Gynecology, McGill University Health Centre, Montreal Quebec, Canada.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Qian
authors.forename: Catherine
authors.initials: C
authors.lastname: Deveault
authors.forename: Rashmi
authors.initials: R
authors.lastname: Bagga
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
authors.forename: Rima
authors.initials: R
authors.lastname: Slim
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D002888:Chromosomes, Human, Pair 19; D018388:Codon, Terminator; D017931:DNA Primers; D005260:Female; D006579:Heterozygote; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D013091:Spermatogenesis / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018388:Codon, Terminator; D017931:DNA Primers; C502448:NLRP7 protein, human