Genetic mapping of a maternal locus responsible for familial hydatidiform moles

Hydatidiform mole (HM) is the product of an aberrant human pregnancy in whi ch there is an abnormal embryonic development and proliferation of placenta l 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 pregn ancies are unknown. We previously postulated that women with recurrent hyda tidiform moles are homozygous for an autosomal recessive defective gene. To map this gene genetically, we initiated a genome-wide scan with highly pol ymorphic short tandem repeats; in individuals from two families with recurr ent HM, Heres, 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 c M interval flanked by D19S924 and D195890. The identification of a gene for HM adds new insights into the molecular genetics of early embryogenesis an d may be relevant to the large number of patients with sporadic HM.