Genetics and Epigenetics of Recurrent Hydatidiform Moles: Basic Science and Genetic Counselling

Ngoc Minh Phuong Nguyen,Rima Slim

doi:10.1007/s13669-013-0076-1

Abstract

Gestational trophoblastic disease (GTD) is a group of conditions that originate from the abnormal hyperproliferation of trophoblastic cells, which derive from the trophectoderm, the outer layer of the blastocyst that would normally develop into the placenta during pregnancy. GTDs encompass hydatidiform mole (HM) (complete and partial), invasive mole, gestational choriocarcinoma, placental-site trophoblastic tumor, and epithelioid trophoblastic tumor. Of these, the most common is HM, and it is the only one that has been reported to recur in the same patients from independent pregnancies, which indicates the patients’ genetic predisposition. In addition, HM is the only GTD that segregates in families according to Mendel’s laws of heredity, which made it possible to use rare familial cases of recurrent HMs (RHMs) to identify two maternal-effect genes, NLRP7 and KHDC3L, responsible for this condition. Here, we recapitulate current knowledge about RHMs and conclude with the role and benefits of testing patients for mutations in the known genes.

Highlights

Hydatidiform mole (HM) is an aberrant human pregnancy with abnormal embryonic development
Higher frequencies of recurrent HMs (RHMs) are reported from the Middle and Far East; in these regions, the frequency of RHMs ranges from 2.5 % up to 9.4 % [6, 15,16,17,18]
We summarize known data about RHMs and highlight the benefits of DNA testing

Summary

Introduction

Hydatidiform mole (HM) is an aberrant human pregnancy with abnormal embryonic development. Other studies examined the methylation status of DMRs in moles from patients with two NLRP7 defective alleles and reported abnormal loss and gain of methylation at some of them [23, 54, 55] In one of these studies, single nucleotide polymorphisms were used to distinguish parental alleles at some imprinted genes and showed that the abnormal methylation, affected the maternal alleles [54] (Table 2). These data demonstrated the presence of imprinting abnormalities in diploid biparental moles from patients with KHDC3L or NLRP7 mutations and

Conclusion

Findings

Conclusions