Recent Advances In Familial Recurrent Hydatidiform Mole

Hydatidiform mole (HM) is an benign trophoblastic disease characterized by trophoblast hyperplasia and interstitial edema of placental villi, including PHM and CHM. The genetic basis in the vast majority of cases is an excess of paternal genome. Although most complete HM are androgenetic in origin, a biparental genomic contribution has been described,it is highly recurrent and frequently familial,named Familial biparental hydatidiform mole (FBHM). The phenotype mimics AnCHM, despite the normal genetic makeup of the conceptus. FBHM is a autosomal recessive disorder,to date,there are almost twenty families have been described.The exact incidence rate of FRHM is unknown,but the recurrence rate and the canceration rate are higher than those patients who have no family history. Through genetics analysis, a major locus have been maped to chromosome19q13.3-19q13.4,even though there is genetic heterogeneity.This region is rich in imprinting genes,includeing CDKN1C, H19, NESP55 et al.Molecular studies have shown that maternal imprinting marks are defected in the BiHM trophoblast.P57kip2,the product of CDKN1C,an incomplete imprinting gene, Fisher et al found dramatic unexpression of P57kip2 in BiHM, similar to that seen in CHM of AnCHM.Several years latter, Kihara found p57kip2 in BiHM and AnCHM are underexpression.Maybe P57kip2 is an candidate gene.DNA methylation marks at imprinted loci have been studied in the BiHM.DNMT is essentialed to establish DNA differentially methylated,included DNMT1,DNMT2,DNMT3. DNMT3L belongs to DNMT3,althouge it has no methyltransferase activity on its own,it can co-operates with DNMT3A to establish imprinting marks. Murdoch et al.used fine mapping found two families with splice site mutations in NALP7 on chromosome 19q13.42 at 2006.Several scholar sequently found several sites mutation of NALP7 which is expressed in a wide variety of nomal and pathological tissues. It belongs to the CATERPILLER family, members of which are commonly involved in inflammatory and apoptotic pathways. NALP7 is the first maternal effect gene identified in human and is also responsible for recurrent spontaneous abortions,stillbirths and intra-uterine growth retardation. We believed that NALP7 is a suprisng BiHM candidate.Now,there are no effective manner to cure FRHM.Although normal pregnancies interspersed with BiHM have been reported in some of the pedigrees,affected women repeatedly attempting pregnancy should be counseled about the risk for invasive trophoblastic disease with each subsequent BiHM. We want to explain the pathogenesis of FRHM,explore genetic treatment prescription and the prognosis.