Report
Intracytoplasmic Sperm Injection May Increase the Risk of Imprinting Defects

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In germ cells and the early embryo, the mammalian genome undergoes widespread epigenetic reprogramming. Animal studies suggest that this process is vulnerable to external factors. We report two children who were conceived by intracytoplasmic sperm injection (ICSI) and who developed Angelman syndrome. Molecular studies, including DNA methylation and microsatellite and quantitative Southern blot analysis, revealed a sporadic imprinting defect in both patients. We discuss the possibility that ICSI may interfere with the establishment of the maternal imprint in the oocyte or pre-embryo.

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The first two authors contributed equally to the work.

Present affiliation: Genzyme Corporation, Cambridge, MA.

Present affiliation: Munich Re, Life Sciences Centre of Competence, Munich.