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. 2003 Jan;72(1):156-60.
doi: 10.1086/346031. Epub 2002 Nov 18.

Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19

Michael R DeBaun  1 , Emily L Niemitz, Andrew P Feinberg
Affiliations

Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19

Michael R DeBaun et al. Am J Hum Genet. 2003 Jan.

Abstract

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.

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Figures

Figure 1
Figure 1
Analysis of methylation at the Lit1 CpG island. Methylation-sensitive Southern blots of LIT1 on DNA from five children with BWS who were conceived using ART and from a normal control (NC). The upper band (6.0 kb) is methylated, and the lower band (4.2 kb) is unmethylated.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. CDC's Reproductive Health Information Source, 1999 Assisted Reproductive Technology Success Rates, http://www.cdc.gov/nccdphp/drh/ART99/99nation.htm
    1. GenBank, http://www.ncbi.nlm.nih.gov/Genbank/ (for human H19 probe [accession number M32053] and human LIT1 probe [accession number AA155639])
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for BWS [MIM 130650], IGF2 [MIM 147470], H19 [MIM 103280], p57KIP2 [MIM 600856], KVLQT1 [MIM 192500], LIT1 [MIM 604115], and Angelman syndrome [MIM 105830])

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