The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients.
Details
Serval ID
serval:BIB_7258B252EAA0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients.
Journal
Modern pathology
ISSN
1530-0285 (Electronic)
ISSN-L
0893-3952
Publication state
Published
Issued date
07/2018
Peer-reviewed
Oui
Volume
31
Number
7
Pages
1116-1130
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Hydatidiform mole is an aberrant human pregnancy characterized by early embryonic arrest and excessive trophoblastic proliferation. Recurrent hydatidiform moles are defined by the occurrence of at least two hydatidiform moles in the same patient. Fifty to eighty percent of patients with recurrent hydatidiform moles have biallelic pathogenic variants in NLRP7 or KHDC3L. However, in the remaining patients, the genotypic types of the moles are unknown. We characterized 80 new hydatidiform mole tissues, 57 of which were from patients with no mutations in the known genes, and we reviewed the genotypes of a total of 123 molar tissues. We also reviewed mutation analysis in 113 patients with recurrent hydatidiform moles. While all hydatidiform moles from patients with biallelic NLRP7 or KHDC3L mutations are diploid biparental, we demonstrate that those from patients without mutations are highly heterogeneous and only a small minority of them are diploid biparental (8%). The other mechanisms that were found to recur in patients without mutations are diploid androgenetic monospermic (24%) and triploid dispermic (32%); the remaining hydatidiform moles were misdiagnosed as moles due to errors in the analyses and/or their unusual mechanisms. We compared three parameters of genetic susceptibility in patients with and without mutations and show that patients without mutations are mostly from non-familial cases, have fewer reproductive losses, and more live births. Our data demonstrate that patients with recurrent hydatidiform moles and no mutations in the known genes are, in general, different from those with mutations; they have a milder genetic susceptibility and/or a multifactorial etiology underlying their recurrent hydatidiform moles. Categorizing these patients according to the genotypic types of their recurrent hydatidiform moles may facilitate the identification of novel genes for this entity.
Keywords
Adaptor Proteins, Signal Transducing/genetics, DNA Mutational Analysis, Female, Genetic Predisposition to Disease, Genotype, Humans, Hydatidiform Mole/genetics, Neoplasms, Second Primary/genetics, Pregnancy, Proteins/genetics, Uterine Neoplasms/genetics
Pubmed
Web of science
Create date
01/03/2018 18:23
Last modification date
20/08/2019 14:30