Familial hydatidiform molar pregnancy: the germline imprinting defect hypothesis?

Imprinting is the uniparental expression of a set of genes. Somatic cells carry two haploid sets of chromosomes, one maternal and one paternal, while germ cells contain only one of the two forms of chromosomes, male or female. This implies that during early embryogenesis the cells committed for developing the future germ cell lineage, the primordial germ cells, which are diploid, have to undergo a total chromosome reprogramming process. This process is delicately controlled during gametogenesis to ensure that males and females have only their respective form of gametes. The machinery involved in this process is yet poorly defined. Familial hydatidiform molar (HM) pregnancy is an abnormal form of pregnancy characterized by hydropic degeneration of placental villi and abnormal, or absence of, embryonic development. To date, the molecular defect causing this condition is unknown. However, in a few studied cases, the presence of paternal methylation patterns on the maternal chromosomes was observed. In this chapter, we summarize what is known about methylation aberrations in HMs and examine more closely the proposed hypothesis of a maternal germline imprinting defect.