Journal
GYNECOLOGIC AND OBSTETRIC INVESTIGATION
Volume 81, Issue 4, Pages 353-358Publisher
KARGER
DOI: 10.1159/000441780
Keywords
Recurrent hydatidiform mole; DNA methylation; NLRP7; Genomic imprinting
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Funding
- Ministry of Health, Labor and Welfare, Japan [H26-082, H26-001, H25-001]
- CREST Program of the Japan Science and Technology Agency (JST)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [26670734, 26293365]
- National Center for Child Health and Development (NCCHD), Japan [26-13]
- Grants-in-Aid for Scientific Research [26670734, 26670169, 25860258, 16K11120, 26293365, 24592494] Funding Source: KAKEN
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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. Ge notyping 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. (C) 2015 S. Karger AG, Basel
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