Genetic mapping of a maternal locus responsible for familial hydatidiform moles

Hydatidiform mole (HM) is the product of an aberrant human pregnancy in which there is an abnormal embryonic development and proliferation of placental villi. The incidence of HM varies between ethnic groups, and occurs in 1 in every 1500 pregnancies in the USA. All HM cases are sporadic, except for extremely rare familial cases. The exact mechanisms leading to molar pregnancies are unknown. We previously postulated that women with recurrent hydatidiform moles are homozygous for an autosomal recessive defective gene. To map this gene genetically, we initiated a genome-wide scan with highly polymorphic short tandem repeats in individuals from two families with recurrent HM. Here, we demonstrate that a defective maternal gene is responsible for recurrent HM. This gene resides on chromosome 19q13.3-13.4 in a 15.2 cM interval flanked by D19S924 and D19S890. The identification of a gene for HM adds new insights into the molecular genetics of early embryogenesis and may be relevant to the large number of patients with sporadic HM.