Human Molecular Genetics, 2003, Vol. 12, No. 12 1405-1413
DOI: 10.1093/hmg/ddg152
© 2003 Oxford University Press
Maternal alleles acquiring paternal methylation patterns in biparental complete hydatidiform moles
1Institute of Experimental Haematology and Transfusion Medicine, Bonn 53105, Germany, 2Department of Obstetrics and Gynecology, American University of Beirut, Beirut PO 11-236, Lebanon, 3Laboratoire génomique des cancers, CNRS UMR 8125, Institut Gustave Roussy, Villejuif F94805, France, 4Institute of Transfusion Medicine and Immune Haematology, Frankfurt 60528, Germany, 5Department of Neurology and 6Departments of Human Genetics and Obstetrics and Gynecology, Montreal General Hospital and McGill University Health Centre, Montreal, Canada H3G 1A4
Received January 27, 2003; Accepted April 20, 2003
We previously mapped a maternal locus responsible for biparental complete hydatidiform moles (BiCHMs) to 19q13.4. The two index patients had a total of 14 molar pregnancies, eight abortions at various developmental stages, and one 16-year-old healthy offspring. We suggested that the defective gene deregulates the expression of imprinted genes. Here, we report the methylation status of four imprinted genes in two BiCHMs from the two sisters, the 16-year-old normal offspring, and two sporadic BiCHMs from unrelated patients. Using two bisulfite-based methods, we demonstrate a general trend of abnormal hypomethylation at the paternally expressed genes, PEG3 and SNRPN, and hypermethylation at the maternally expressed genes, NESP55 and H19, in two to four BiCHMs. Using single nucleotide polymorphisms, we provide the first evidence that SNRPN, NESP55 and H19 are abnormally methylated on the maternal alleles in BiCHMs. We show, in the BiCHMs from the two sisters, that the abnormally methylated H19 allele is inherited from either the maternal grandmother or the maternal grandfather. These data suggest that the abnormal methylation in BiCHMs is not due to an error in erasing the parental imprinting marks but rather in the re-establishment of the new maternal marks during oogenesis or their postzygotic maintenance. The defective 19q13.4 locus may have led to the development of variable degrees of ‘faulty’ paternal marks on the maternal chromosomes.
* To whom correspondence should be addressed at: Montreal General Hospital Research Institute, room L12-132, 1650 Cedar Avenue, Montreal, Canada H3G 1A4. Tel: +1 5149341934, ext 44519; Fax: +1 5149348265; Email: rima.slim{at}muhc.mcgill.ca
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