Novel Nonsense Mutation in the NLRP7 Gene Associated with Recurrent Hydatidiform Mole

Yuki Ito, Kayoko Maehara, Eisuke Kaneki, Kentaro Matsuoka, Naoko Sugahara, Tomoko Miyata, Hiromi Kamura, Yuko Yamaguchi, Ayako Kono, Kazuhiko Nakabayashi, Ohsuke Migita, Ken Higashimoto, Hidenobu Soejima, Aikou Okamoto, Hitomi Nakamura, Tadashi Kimura, Norio Wake, Takeshi Taniguchi, Kenichiro Hata

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Aim: This study aimed to clarify the genetic and epigenetic features of recurrent hydatidiform mole (RHM) in Japanese patients. Methods: Four Japanese isolated RHM cases were analyzed using whole-exome sequencing. Villi from RHMs were collected by laser microdissection for genotyping and DNA methylation assay of differentially methylated regions (DMRs). Single nucleotide polymorphisms of PEG3 and H19 DMRs were used to confirm the parental origin of the variants. Results: A novel homozygous nonsense mutation in NLRP7 (c.584G>A; p.W195X) was identified in 1 patient. Genotyping of one of her molar tissue revealed that it was biparental but not androgenetic in origin. Despite the fact that the RHM is biparental, maternally methylated DMRs of PEG3, SNRPN and PEG10 showed complete loss of DNA methylation. A paternally methylated DMR of H19 retained normal methylation. Conclusions: This is the first Japanese case of RHM with a novel homozygous nonsense NLRP7 mutation and a specific loss of maternal DNA methylation of DMRs. Notably, the mutation was identified in an isolated case of an ethnic background that has not previously been studied in this context. Our data underscore the involvement of NLRP7 in RHM pathophysiology and confirm that DNA methylation of specific regions is critical.

Original languageEnglish
Pages (from-to)353-358
Number of pages6
JournalGynecologic and Obstetric Investigation
Volume81
Issue number4
DOIs
Publication statusPublished - Jul 1 2016

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynaecology

Cite this