Comprehensive genotype phenotype correlations between NLRP7 mutations and the balance between embryonic tissue differentiation and trophoblastic proliferation

Hydatidiform mole (HM) is a human pregnancy with no embryo, but excessive trophoblastic proliferation. Maternal recessive mutationsin NLRP7 are responsible for recurrent HMs, which are characterized by diploid biparental genomes, abnormal DNA methylation, and absence of p57^Kip2 expression, the protein coded by the imprinted CDKN1C gene. In this study, we demonstrate a strong correlation between the nature of NLRP7 mutations in the patients and the phenotypical features of their HMs. Protein-truncating mutations repress p57^KIP2 expression and are associated with the absence of embryonic tissues and excessive trophoblastic proliferation. However, some missense mutations do not completely repress p57^KIP2 expression and are associated with the presence of embryonic tissues and mild trophoblastic proliferation. Our data suggest a novel role for NLRP7in regulating the balance between tissue differentiation and proliferation during early development. (By Ngoc Minh Phuong Nguyen, http://jmg.bmj.com/content/early/2014/08/05/jmedgenet-2014-102546 )