Mutations and genetic variants of NLRP7 have been found in women with infertility associated conditions, such as recurrent hydatidiform mole, recurrent miscarriage, and preeclampsia.
In order to better understand how the effects of HYDM1 are associated with mutations on the structure of NLRP7, we performed an inter-domain interaction screen using a yeast two-hybrid system.
In this study, we characterised the expression of the imprinted, maternally expressed gene, CDKN1C (p57(KIP2)), the genotype, and the histopathology of 36 products of conception (POC) from patients with two defective alleles in NLRP7 and looked for potential correlations between the nature of the mutations in the patients and the various HM features.
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 compared with women with no family history of mole or miscarriage.
The p.L750V mutation in the NLRP7 gene is frequent in Mexican patients with recurrent molar pregnancies and is not associated with recurrent pregnancy loss.
As homozygous NLRP7 mutations are associated with recurrent hydatidiform mole or conception loss, the heterozygous state could represent a risk factor for nonrecurrent mole.
To understand the mechanisms leading to hydatidiform mole formation in patients with NLRP7 mutations, we used a combination of various approaches to characterize five products of conception, from two patients, shown by flow cytometry to contain non-diploid cells.
To investigate the role of NLRP7 in sporadic moles and other forms of reproductive wastage, the authors sequenced this gene in a cohort of 135 patients with at least one hydatidiform mole or three spontaneous abortions; 115 of these were new patients.
A familial or sporadic recurrent hydatidiform mole is a rare autosomal recessive condition that has been associated with biallelic mutations in the nucleotide-binding, leucine-rich repeat, pyrin domain 7 (NLRP7) gene (19q13.42).
While germline mutations in NLRP7 have previously been associated with familial hydatidiform mole, this is the first description of NLRP2 mutation in human disease and the first report of a trans mechanism for disordered imprinting in BWS.