Biparental hydatidiform moles: a maternal effect mutation affecting imprinting in the offspring

Hum Reprod Update. 2006 May-Jun;12(3):233-42. doi: 10.1093/humupd/dmk005. Epub 2006 Mar 15.

Abstract

Highly recurrent hydatidiform moles (HMs) studied to date are not androgenetic but have biparental genomic contribution (BiHM). Affected women have an autosomal recessive mutation that causes their pregnancies to develop into HM. Although there is genetic heterogeneity, a major locus maps to chromosome 19q13.42, but a mutated gene has not yet been identified. Molecular studies have shown that maternal imprinting marks are deregulated in the BiHM trophoblast. The mutations that cause this condition are, therefore, hypothesized to occur in genes that encode transacting factors required for the establishment of imprinting marks in the maternal germline or for their maintenance in the embryo. Although only DNA methylation marks at imprinted loci have been studied in the BiHM, the mutation may affect genes that are essential for other forms of chromatin remodelling at imprinted loci and necessary for correct maternal allele-specific DNA methylation and imprinted gene expression. Normal pregnancies interspersed with BiHM have been reported in some of the pedigrees, but affected women repeatedly attempting pregnancy should be counselled about the risk for invasive trophoblastic disease with each subsequent BiHM.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Chromatin / metabolism
  • DNA Methylation
  • Female
  • Genes, Recessive / genetics*
  • Genomic Imprinting*
  • Humans
  • Hydatidiform Mole / classification
  • Hydatidiform Mole / diagnosis
  • Hydatidiform Mole / genetics*
  • Mutation
  • Pregnancy
  • Pregnancy Complications / genetics*
  • Uterine Neoplasms / classification
  • Uterine Neoplasms / diagnosis
  • Uterine Neoplasms / genetics*

Substances

  • Chromatin