Detection of altered methylation status at 11p15.5 and 7q32 in placental mesenchymal dysplasia.
OBJECTIVE
This paper aims to present molecular cytogenetic and epigenetic evaluation of placental mesenchymal dysplasia (PMD).


METHODS
A 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.


RESULTS
MS-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.


CONCLUSIONS
MS-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.
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: cpc_mmh@yahoo.com.
Chih-Ping
CP
Chen
Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Yi-Ning
YN
Su
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
Ming-Huei
MH
Lin
Department of Pathology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
Tao-Yeuan
TY
Wang
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
Schu-Rern
SR
Chern
Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yu-Ling
YL
Kuo
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
Yu-Ting
YT
Chen
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Bioengineering, Tatung University, Taipei, Taiwan.
Wayseen
W
Wang
D000328:Adult; D002880:Chromosomes, Human, Pair 11; D002897:Chromosomes, Human, Pair 7; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000000981:diagnostic imaging / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008648:Mesoderm / Q000000981:diagnostic imaging / Q000473:pathology; D009030:Mosaicism; D010920:Placenta / Q000000981:diagnostic imaging / Q000473:pathology*; D010922:Placenta Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D016216:Ultrasonography, Prenatal; D014594:Uterine Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics*
androgenetic/biparental mosaicism; methylation-specific multiplex ligation-dependent probe amplification; methylation-specific polymerase chain reaction; placental mesenchymal dysplasia; quantitative fluorescent polymerase chain reaction