Heterogeneity in recurrent complete hydatidiform mole: Presentation of two new Turkish families with different genetic characteristics

Abstract

Subsequent pregnancy outcomes following complete hydatidiform moles (CHM) are usually favorable and the risk of a second CHM less than 2%. However, a small number of women have a rare autosomal recessive condition that predisposes them to CHM. Unlike typical CHM, that are androgenetic (AnCHM), the CHM in these women are diploid and biparental (BiCHM) with a contribution from each parent to the nuclear genome. To date most women with recurrent CHM have been found to have BiCHM and to have a wide variety of mutations in the causative gene, NLRP7. Our objectives were to genotype the molar tissue and identify the NLRP7 mutations in two unrelated Turkish women with recurrent CHM. Fluorescent microsatellite genotyping of molar tissue and screening of patient DNA for NLRP7 mutations was carried out in two women with five and four CHM respectively. The first case was confirmed to have BiCHM. In addition the patient was found to have a novel homozygous mutation in exon 8 of NLRP7. All CHM examined in the second case were AnCHM and no NLRP7 mutations were identified in DNA from the patient. This report describes a further individual with BiCHM and a novel mutation in NLRP7. A second patient with similar clinical history had no mutations in NLRP7 and is the first report of a patient with four CHM where the CHM are androgenetic. This study highlights the heterogeneity of recurrent CHM and the need to investigate women with recurrent molar pregnancies for appropriate clinical management.