A global disorder of imprinting in the human female germ line

Nature. 2002 Apr 4;416(6880):539-42. doi: 10.1038/416539a.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Consanguinity
  • DNA Methylation
  • Female
  • Genetic Markers
  • Genomic Imprinting*
  • Humans
  • Hydatidiform Mole / genetics*
  • Male
  • Mutation
  • Oocytes*
  • Ovarian Neoplasms / genetics*
  • Polymerase Chain Reaction
  • Pregnancy
  • Sulfites


  • Genetic Markers
  • Sulfites