The genetics of hydatidiform moles: new lights on an ancient disease

Abstract

Hydatidiform mole (HM) is a human pregnancy with no embryo but cystic degeneration of chorionic villi. The common form of this condition occurs in 1 in every 1500 pregnancies in western societies and at a higher incidence in some geographic regions and populations. Recurrent moles account for 2% of all molar cases and a few of them occur in more than one family member. By studying a familial form of recurrent moles, a recessive maternal locus responsible for this condition was mapped to 19q13.4 and causative mutations identified. The defective protein, NALP7, is part of the CATERPILLAR protein family with roles in pathogen-induced inflammation and apoptosis. The exact role of NALP7 in the pathophysiology of molar pregnancies is unknown yet. NALP7 could have a role either in oogenesis or in the endometrium during trophoblast invasion and decidualization. In this review, we outlined recent advances in the field of HMs and reviewed the literature in the light of the new data.

Mosaics and moles

“…Usually, a substantial correlation between phenotype and genotype is reported (CHMs mostly being diploid, and PHMs mostly being triploid). 1 However, possibly the criteria for the morphologic subclassification of HMs are not optimal for the rare DiAnd/BiparHMs and DiBiparHMs. Also, at least for the mosaics, the selection of tissue for examination may influence the diagnosis made.…”

“…Fewer DiAndHMs show heterozygosity in some loci as if an empty oocyte was fertilized by two independent spermatozoa from the same father. 1 However, over the years, diploid HMs with biparental contributions to the genome have been reported. [2][3][4][5][6][7] A molar phenotype in a diploid conceptus with biparental alleles may be caused by paternal methylation patterns on maternally inherited chromosomes.…”

Molar pregnancy and childhood cancer: a population-based linkage study from Denmark

“…Both childhood cancer and hydatidiform mole (HMs) are rare conditions with around 1 in 600 children likely to develop cancer before they are 15 years old (Parkin et al, 1998) and HM likely to occur in 1 in 1500 pregnancies in the western world (Altieri et al, 2003). Hydatidiform moles generally arise from an abnormal fertilisation and have been associated with the de-regulation of imprinted genes (Altieri et al, 2003;Slim and Mehio, 2007). Thus, while epigenetics is not a new concept with respect to the pathogenesis of HM (Kajii and Ohama, 1977), for childhood cancer it is a relatively new and expanding area of research.…”

“…Recent work has identified NALP7, part of the CATERPILLAR family of proteins that are involved in cellular inflammatory responses to infections processes, as the gene causing familial recurrent HMs (Tschopp et al, 2003;Murdoch et al, 2006). While its exact role in familial recurrent HMs are unknown, for example it has no established role in DNA methylation, there have been several possible biological mechanisms put forward (Slim and Mehio, 2007). The most interesting of these in relation to childhood cancer, in particular childhood leukaemia, is the involvement of NALP7 in the cellular immune response.…”

“…The most interesting of these in relation to childhood cancer, in particular childhood leukaemia, is the involvement of NALP7 in the cellular immune response. An abnormal immune relationship between a mother and a fetus has been associated with irregular pregnancy outcomes such as HM and choriocarcinoma (reviewed by Slim and Mehio, 2007). Thus insight into the aetiology of some childhood cancers may be gained by investigating the immune function and response of mothers of children with such conditions.…”