The maternally transcribed gene p57KIP2 (CDNK1C) is abnormally expressed in both androgenetic and biparental complete hydatidiform moles

Hydatidiform mole (HM) is an abnormal gestation characterized by trophoblast hyperplasia and overgrowth of placental villi. The genetic basis in the vast majority of cases is an excess of paternal to maternal genomes, suggesting that global misexpression of imprinted genes is the common molecular mechanism underlying the genesis of this condition. Although most complete HM are androgenetic in origin, a rare, frequently familial, biparental variant has been described. Here we evaluate the expression of p57(KIP2), the product of CDKN1C, an imprinted, maternally expressed gene in a series of these rare, biparental complete HM (BiCHM). We observed dramatic underexpression of p57(KIP2) in BiCHM, identical to that seen in complete HM of androgenetic origin (AnCHM). The series included two sisters, both of whom had BiCHM. Genotyping of this family identified a 15 cM region of homozygosity for 19q13.3-13.4 similar to that found in three other families with recurrent BiCHM. These results demonstrate that BiCHM, like AnCHM, result from abnormal expression of imprinted genes. In addition we provide further evidence for a major control gene on 19q13.3-13.4 which regulates expression of imprinted genes on other chromosomes.