Intracytoplasmic sperm injection (ICSI) was introduced as a solution to male infertility, but some investigators have found that it could be associated with an increased risk of birth defects, and also to a higher incidency of aneuploidies. In this paper, authors report two cases of unrelated children who where conceived by ICSI that were affected by Angelman syndrome (AS), a neurological disorder with genetic or epigenetic origin, caused by mutation or loss of imprinting in the UBE3A gene. The two patients studied were girls that showed abnormal methylation patterns in a Southern analysis using the SNRPN probe, and this was confirmed by MSP. This report led the authors to hypothesize that ICSI was causally related to the imprinting defect, based on these facts: (1) AS is a rare disease; (2) maternal methylation imprint on chromosome 15 is only established after fertilization; (3) ICSI bypasses many of the normal steps involved in fertilization, and besides, the oocyte undergoes mechanical stress; and (4) some investigations in sheep have shown association between fetal overgrowth and hypomethylation of the Igf2r allele. These observations were later confirmed in studies of related diseases, for example the Prader-Willi syndrome (PWS).
Cox, GF. et al. 2002. Am J Hum Genet 71(1): 162–164
epigenetics
Cox, GF. et al. 2002. Am J Hum Genet 71(1): 162–164
epigenetics
