Genomic imprinting in gestational trophoblastic disease--a review

The abnormal pregnancy hydatidiform mole (HM) can be classified as complete (CHM) or partial (PHM) on the basis of both morphology and genetic origin. PHM are diandric triploids while almost all CHM are androgenetic. Thus the characteristic trophoblastic hyperplasia seen in both CHM and PHM is usually associated with the presence of two paternal genomes. Very occasionally CHM may be diploid, but biparental, in origin. These rare BiCHM are found in patients with recurrent HM and appear to be associated with an autosomal recessive condition predisposing to molar pregnancies. Since they are pathologically indistinguishable from androgenetic CHM, BiCHM are also likely to result from defects in genomic imprinting. There is evidence that the gene mutated in this condition, provisionally mapped to 19q13.3-13.4, may be important in setting the maternal imprint in the ovum. Women with BiCHM have a much higher risk of recurrent HM than women with AnCHM and an appreciable risk of persistent trophoblastic disease. Investigation of these unusual BiCHM and isolation of the defective gene will lead to a greater understanding of the function of genomic imprinting in early development.