A global disorder of imprinting in the human female germ line.
Imprinted genes are expressed differently depending on whether they are carried by a chromosome of maternal or paternal origin. Correct imprinting is established by germline-specific modifications; failure of this process underlies several inherited human syndromes. All these imprinting control defects are cis-acting, disrupting establishment or maintenance of allele-specific epigenetic modifications across one contiguous segment of the genome. In contrast, we report here an inherited global imprinting defect. This recessive maternal-effect mutation disrupts the specification of imprints at multiple, non-contiguous loci, with the result that genes normally carrying a maternal methylation imprint assume a paternal epigenetic pattern on the maternal allele. The resulting conception is phenotypically indistinguishable from an androgenetic complete hydatidiform mole, in which abnormal extra-embryonic tissue proliferates while development of the embryo is absent or nearly so. This disorder offers a genetic route to the identification of trans-acting oocyte factors that mediate maternal imprint establishment.
Judson
Hannah
H
University of Leeds, Molecular Medicine Unit, St. James's University Hospital, UK.
Hayward
Bruce E
BE
Sheridan
Eamonn
E
Bonthron
David T
DT
D000328:Adult; D003241:Consanguinity; D019175:DNA Methylation; D005260:Female; D005819:Genetic Markers; D018392:Genomic Imprinting; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics*; D008297:Male; D009154:Mutation; D009865:Oocytes; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D013447:Sulfites
D005819:Genetic Markers; D013447:Sulfites