• biparental hydatidiform mole
• genomic imprinting
• chromosome 19q13,4

Hydatidiform mole (HM) is an uncommon type of pregnancy, typically resulting from a diandric conception. HM may be defined as complete (CHM), having an androgenetic, diploid genome (AnCHM),^1,2 or partial, having a diandric, triploid genome (PHM).^3,4 A rare type of CHM is diploid but, unlike AnCHM, is biparental (BiCHM) in origin.^5,6 It has been shown that AnCHM and BiCHM are pathologically indistinguishable,⁷ such that the pathology of BiCHM is also likely to involve the misexpression of imprinted genes.⁸

Genomic imprinting has recently been investigated in BiCHM tissue. In one case of recurrent BiCHM, five maternally set, imprinted genes were shown to have a paternal methylation pattern in the molar tissue, while H19, a paternally set, imprinted gene, had a normal pattern of methylation.⁹ A series of BiCHM from several patients have also been examined for expression of the CDKN1C gene that is dependent on a maternally set imprint of the KvDMR1 control centre.¹⁰ The CDKN1C gene product, p57^KIP2, was not expressed in AnCHM tissue as would be predicted from their purely paternal genome. However, the p57^KIP2 protein was also absent from BiCHM samples despite the presence of a maternal genome, implying failure to set the maternal imprint for CDKN1C (KvDMR1).¹¹ These two studies show that the BiCHM gene is associated with a loss of maternal imprints within the ovum, which is not limited to one locus, as is the case with other genes that regulate imprinting in cis. Instead, the BiCHM gene may act as a major regulator of imprinting and act in trans throughout the genome.