Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/108383
Title: Absence of Maternal Methylation in Biparental Hydatidiform Moles from Women with NLRP7 Maternal-Effect Mutations Reveals Widespread Placenta-Specific Imprinting
Author: Sanchez-Delgado, Marta
Martin-Trujillo, Alejandro
Tayama, Chiharu
Vidal, Enrique
Esteller, Manel
Iglesias Platas, Isabel
Deo, Nandita
Barney, Olivia
Maclean, Ken
Hata, Kenichiro
Nakabayashi, Kazuhiko
Fisher, Rosemary
Monk, David
Keywords: Metilació
ADN
Mola hidatídica
Placenta
Genòmica
Mutació (Biologia)
Embaràs
Methylation
DNA
Hydatidiform mole
Placenta
Genomics
Mutation (Biology)
Pregnancy
Issue Date: 6-Nov-2015
Publisher: Public Library of Science (PLoS)
Abstract: Familial recurrent hydatidiform mole (RHM) is a maternal-effect autosomal recessive disorder usually associated with mutations of the NLRP7 gene. It is characterized by HM with excessive trophoblastic proliferation, which mimics the appearance of androgenetic molar conceptuses despite their diploid biparental constitution. It has been proposed that the phenotypes of both types of mole are associated with aberrant genomic imprinting. However no systematic analyses for imprinting defects have been reported. Here, we present the genome-wide methylation profiles of both spontaneous androgenetic and biparental NLRP7 defective molar tissues. We observe total paternalization of all ubiquitous and placentaspecific differentially methylated regions (DMRs) in four androgenetic moles; namely gain of methylation at paternally methylated loci and absence of methylation at maternally methylated regions. The methylation defects observed in five RHM biopsies from NLRP7 defective patients are restricted to lack-of-methylation at maternal DMRs. Surprisingly RHMs from two sisters with the same missense mutations, as well as consecutive RHMs from one affected female show subtle allelic methylation differences, suggesting inter-RHM variation. These epigenotypes are consistent with NLRP7 being a maternal-effect gene and involved in imprint acquisition in the oocyte. In addition, bioinformatic screening of the resulting methylation datasets identified over sixty loci with methylation profiles consistent with imprinting in the placenta, of which we confirm 22 as novel maternally methylated loci. These observations strongly suggest that the molar phenotypes are due to defective placenta-specific imprinting and over-expression of paternally expressed transcripts, highlighting that maternal-effect mutations of NLRP7 are associated with the most severe form of multi-locus imprinting defects in humans.
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pgen.1005644
It is part of: PLoS Genetics, 2015, vol. 11, num. 11, p. 1-17
Related resource: https://doi.org/10.1371/journal.pgen.1005644
URI: http://hdl.handle.net/2445/108383
ISSN: 1553-7390
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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