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@article{Sanchez-Delgado:2015:10.1371/journal.pgen.1005644,
author = {Sanchez-Delgado, M and Martin-Trujillo, A and Tayama, C and Vidal, E and Esteller, M and Iglesias-Platas, I and Deo, N and Barney, O and Maclean, K and Hata, K and Nakabayashi, K and Fisher, R and Monk, D},
doi = {10.1371/journal.pgen.1005644},
journal = {PLOS Genetics},
title = {Absence of Maternal Methylation in Biparental Hydatidiform Moles from Women with NLRP7 Maternal-Effect Mutations Reveals Widespread Placenta-Specific Imprinting},
url = {http://dx.doi.org/10.1371/journal.pgen.1005644},
volume = {11},
year = {2015}
}

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TY  - JOUR
AB  - Familial recurrent hydatidiform mole (RHM) is a maternal-effect autosomal recessive disorderusually associated with mutations of the NLRP7 gene. It is characterized by HM withexcessive trophoblastic proliferation, which mimics the appearance of androgenetic molarconceptuses despite their diploid biparental constitution. It has been proposed that the phenotypesof both types of mole are associated with aberrant genomic imprinting. However nosystematic analyses for imprinting defects have been reported. Here, we present thegenome-wide methylation profiles of both spontaneous androgenetic and biparental NLRP7defective molar tissues. We observe total paternalization of all ubiquitous and placentaspecificdifferentially methylated regions (DMRs) in four androgenetic moles; namely gain ofmethylation at paternally methylated loci and absence of methylation at maternally methylatedregions. The methylation defects observed in five RHM biopsies from NLRP7 defectivepatients are restricted to lack-of-methylation at maternal DMRs. Surprisingly RHMs fromtwo sisters with the same missense mutations, as well as consecutive RHMs from oneaffected female show subtle allelic methylation differences, suggesting inter-RHM variation.These epigenotypes are consistent with NLRP7 being a maternal-effect gene and involvedin imprint acquisition in the oocyte. In addition, bioinformatic screening of the resulting methylation datasets identified over sixty loci with methylation profiles consistent withimprinting 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-specificimprinting and over-expression of paternally expressed transcripts, highlightingthat maternal-effect mutations of NLRP7 are associated with the most severe form ofmulti-locus imprinting defects in humans.
AU  - Sanchez-Delgado,M
AU  - Martin-Trujillo,A
AU  - Tayama,C
AU  - Vidal,E
AU  - Esteller,M
AU  - Iglesias-Platas,I
AU  - Deo,N
AU  - Barney,O
AU  - Maclean,K
AU  - Hata,K
AU  - Nakabayashi,K
AU  - Fisher,R
AU  - Monk,D
DO  - 10.1371/journal.pgen.1005644
PY  - 2015///
SN  - 1553-7390
TI  - Absence of Maternal Methylation in Biparental Hydatidiform Moles from Women with NLRP7 Maternal-Effect Mutations Reveals Widespread Placenta-Specific Imprinting
T2  - PLOS Genetics
UR  - http://dx.doi.org/10.1371/journal.pgen.1005644
UR  - http://hdl.handle.net/10044/1/27815
VL  - 11
ER  -

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