Prenatal diagnosis of hypomethylation at KvDMR1 and Beckwith-Wiedemann syndrome in a pregnancy conceived by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer.
OBJECTIVE
We report prenatal diagnosis of hypomethylation at KvDMR1 and Beckwith-Wiedemann syndrome (BWS) in a pregnancy conceived by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer.


METHODS
A 34-year-old, primigravid woman was referred to the hospital at 21 weeks' gestation because of advanced maternal age and an isolated omphalocele in the fetus. Her husband had the fertility problem of oligospermia. This pregnancy was achieved by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer. Prenatal ultrasound revealed a 2.1 cm × 1.6 cm isolated omphalocele. The woman underwent amniocentesis. Array comparative genomic hybridization and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were applied to the DNA extracted from the uncultured amniocytes. Conventional cytogenetic analysis and high-resolution melting analysis were performed on cultured amniocytes. Array comparative genomic hybridization revealed no genomic imbalance. MS-MLPA analysis revealed H19DMR(IC1) normal methylation and KvDMR1(IC2) hypomethylation. Conventional cytogenetic analysis revealed a karyotype of 46,XX. High-resolution melting analysis using a methylation-specific polymerase chain reaction assay confirmed normal methylation at H19DMR(IC1) and hypomethylation at KvDMR1(IC2). The altered methylation status at 11p15.5 and the phenotype of omphalocele were consistent with the diagnosis of BWS.


CONCLUSIONS
In case of prenatally detected omphalocele associated with an obstetric history of assisted reproductive technology, a differential diagnosis of BWS should be considered. Methylation assays such as MS-MLPA and methylation-specific polymerase chain reaction using uncultured amniocytes are useful for rapid diagnosis of BWS under such circumstances.
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, National Taiwan University Hospital, Taipei, Taiwan.
Shee-Uan
SU
Chen
Taiji Fetal Medicine Center, Taipei, Taiwan.
Tung-Yao
TY
Chang
Taiji Fetal Medicine Center, Taipei, Taiwan.
Pei-Chen
PC
Wu
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
Schu-Rern
SR
Chern
Gene Biodesign Co. Ltd, Taipei, Taiwan.
Peih-Shan
PS
Wu
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; Department of Bioengineering, Tatung University, Taipei, Taiwan.
Wayseen
W
Wang
D000328:Adult; D001506:Beckwith-Wiedemann Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*; D019175:DNA Methylation; D003937:Diagnosis, Differential; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D006554:Hernia, Umbilical / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D008297:Male; D009845:Oligospermia / Q000628:therapy; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic; D016216:Ultrasonography, Prenatal
C485621:KCNQ1OT1 long non-coding RNA, human; D024642:Potassium Channels, Voltage-Gated
Beckwith–Wiedemann syndrome; KvDMR1; intracytoplasmic sperm injection; in vitro fertilization and embryo transfer; prenatal diagnosis