Detection of altered methylation status at 11p15.5 and 7q32 in placental mesenchymal dysplasia

ObjectiveThis paper aims to present molecular cytogenetic and epigenetic evaluation of placental mesenchymal dysplasia (PMD).Materials and methodsA 33-year-old woman was referred to the hospital at 18 weeks of gestation because of a multicystic mass in the placenta. Ultrasound showed a normal amount of amniotic fluid and a normal singleton fetus. Amniocentesis revealed a karyotype of 46,XX. Array comparative genomic hybridization analysis of amniocytes revealed no genomic imbalance. Preterm labor and premature rupture of the membranes occurred, and a female fetus was delivered with no structural abnormality. The placenta was enlarged and filled with many grape-like vesicles. In the placental cystic mass, interphase fluorescence in situ hybridization revealed diploidy and array comparative genomic hybridization revealed no genomic imbalance. Quantitative fluorescent polymerase chain reaction (QF-PCR), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), and methylation-specific PCR were performed in the placental cystic mass.ResultsMS-MLPA analysis showed hypermethylation (methylation index = 0.8) at H19 differentially methylated region (DMR) [imprinting center 1 (IC1)] at 11p15.5 and hypomethylation (methylation index = 0.2) at KvDMR1(IC2) at 11p15.5. Methylation-specific PCR assay identified hypomethylation of PEG1/MEST at 7q32, and hypermethylation at H19DMR and hypomethylation at KvDMR1 at 11p15.5. QF-PCR analysis identified androgenetic/biparental mosaicism in the placenta. The placental cystic mass was consistent with the diagnosis of PMD.ConclusionMS-MLPA and methylation-specific PCR are useful methods for rapid detection of epigenetic alternations in PMD, and QF-PCR is useful in the diagnosis of androgenetic/biparental mosaicism.