title: Novel Nonsense Mutation in the NLRP7 Gene Associated with Recurrent Hydatidiform Mole.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Kayoko
authors.initials: K
authors.lastname: Maehara
authors.forename: Eisuke
authors.initials: E
authors.lastname: Kaneki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Naoko
authors.initials: N
authors.lastname: Sugahara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miyata
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kamura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Ayako
authors.initials: A
authors.lastname: Kono
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Ohsuke
authors.initials: O
authors.lastname: Migita
authors.forename: Ken
authors.initials: K
authors.lastname: Higashimoto
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Soejima
authors.forename: Aikou
authors.initials: A
authors.lastname: Okamoto
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
authors.forename: Norio
authors.initials: N
authors.lastname: Wake
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics*; D007564:Japan; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D014594:Uterine Neoplasms / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018389:Codon, Nonsense; C502448:NLRP7 protein, human