Mutations in NLRP5 are associated with reproductive wastage and multi-locus imprinting disorders in humans

Some imprinting disorders have higher than expected prevalence of monozygotic twinning, of assisted reproductive technology among parents, and of disturbance of multiple imprinted loci, for which few causative trans-acting mutations have been found.

Here we report mutations in NLRP5 in five mothers of individuals affected by multi-locus imprinting disturbance. Maternal-effect mutations of other human NLRP genes, NLRP7 and NLRP2, cause familial biparental hydatidiform mole and multi-locus imprinting disturbance respectively. Offspring of mothers with NLRP5 mutations have heterogeneous clinical and epigenetic features, but cases include a discordant monozygotic twin pair, individuals with idiopathic developmental delay and autism, and families affected by infertility and reproductive wastage.