title: Genetic and epigenetic analysis of recurrent hydatidiform mole.
abstract: Familial biparental hydatidiform mole (FBHM) is a maternal-effect autosomal recessive disorder in which recurrent pregnancy failure with molar degeneration occurs. The phenotype mimics molar pregnancy due to androgenesis, despite the normal genetic makeup of the conceptus. FBHM appears to result from a failure to establish correct maternal epigenetic identity at imprinted loci during oogenesis. Several women affected with FBHM have previously been shown to have biallelic mutations in the NLRP7 gene (NALP7). Here, we present the results of epigenetic and mutational analysis on FBHM patients from 11 families, 10 of them novel. We demonstrate a methylation defect at imprinted loci in tissue from four new FBHM cases. Biallelic NLRP7 mutations, including eight previously undescribed mutations, were found in all but one family. These results indicate for the first time that maternal imprints at some loci may be correctly specified in FBHM conceptions, since differential methylation of SGCE/PEG10 was preserved in all four cases.
authors.affiliation: Leeds Institute of Molecular Medicine, University of Leeds, UK.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Hayward
authors.forename: Michel
authors.initials: M
authors.lastname: De Vos
authors.forename: Nargese
authors.initials: N
authors.lastname: Talati
authors.forename: M Reza
authors.initials: MR
authors.lastname: Abdollahi
authors.forename: Graham R
authors.initials: GR
authors.lastname: Taylor
authors.forename: Esther
authors.initials: E
authors.lastname: Meyer
authors.forename: Denise
authors.initials: D
authors.lastname: Williams
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.forename: Faridon
authors.initials: F
authors.lastname: Setna
authors.forename: Kausar
authors.initials: K
authors.lastname: Nazir
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Hussaini
authors.forename: Hussain
authors.initials: H
authors.lastname: Jafri
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Rashid
authors.forename: Eamonn
authors.initials: E
authors.lastname: Sheridan
authors.forename: David T
authors.initials: DT
authors.lastname: Bonthron
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D014594:Uterine Neoplasms / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C502448:NLRP7 protein, human