Evidence of a genetic heterogeneity of familial hydatidiform moles.

We previously mapped a maternal recessive locus responsible for familial hydatidiform moles (HMs) to 19q13.4. The candidate region has recently been narrowed down to 1.1 megabases. Here, we report the segregation of alleles at 18 genetic markers, including nine new ones, from the HMs candidate region in a recently reported consanguineous family. In this family, five affected women had a total of seven HMs, three miscarriages, and three normal children. Linkage and haplotype analyses exclude linkage to 19q13.4 and indicate the presence of a second recessive locus responsible for familial molar pregnancies. The heterogeneity in the phenotype of the conceptuses of patients with familial HMs is in agreement with previous observations and seems to be a common feature of this condition. This indicates that the homozygous genetic defects leading to hydatidiform moles can be modulated by other genetic or environmental factors. The identification of these factors may unravel natural ways to treat these forms of reproductive wastage and reverse the infertility of women with recurrent moles.