Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19.
Recent data in humans and animals suggest that assisted reproductive technology (ART) might affect the epigenetics of early embryogenesis and might cause birth defects. We report the first evidence, to our knowledge, that ART is associated with a human overgrowth syndrome-namely, Beckwith-Wiedemann syndrome (BWS). In a prospective study, the prevalence of ART was 4.6% (3 of 65), versus the background rate of 0.8% in the United States. A total of seven children with BWS were born after ART-five of whom were conceived after intracytoplasmic sperm injection. Molecular studies of six of the children indicate that five of the six have specific epigenetic alterations associated with BWS-four at LIT1 and one at both LIT1 and H19. We discuss the implications of our finding that ART is associated with human overgrowth, similar to the large offspring syndrome reported in ruminants.
DeBaun
Michael R
MR
Division of Pediatric Hematology-Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, USA.
Niemitz
Emily L
EL
Feinberg
Andrew P
AP
D000328:Adult; D001506:Beckwith-Wiedemann Syndrome / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D002648:Child; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*
C094335:H19 long non-coding RNA; C449939:KCNQ1OT1 RNA; C485621:KCNQ1OT1 long non-coding RNA, human; D008565:Membrane Proteins; D024642:Potassium Channels, Voltage-Gated; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated