Gene- and Imprintdefects in patients withmit Prader-Willi and Angelman syndrome

The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are distinct neurogenetic disorders which are caused by the loss of function of imprinted genes in 15q11-q13. Our project focuses on the analysis of imprinting defects in PWS and AS and the identification of genes affected in PWS. In the previous funding period we found that a particular imprinting centre haplotype as well as homozygosity for the frequent MTHFR 677C>T mutation increase the risk of maternal imprinting defects. We will now determine the MTHFR-genotype and folate dependent rate of imprinting maintenance defects in fibroblasts. Second, we will examine the role of the transcriptional repressor TIEG1, which we have found to bind to the AS-SRO element of the imprinting centre, in maternal imprinting. We will isolate oocyte-specific binding partners of TIEG1 and perform DNA methylation studies in the offspring of female Tieg1-/- mice. Third, we will characterize novel genes in the PWS region that we have recently identified.
Keywords: Imprinting
Domain: Human Genetics, genomic imprinting
Involved in the project: Hülya Nazlican, PhD
Michaela Wawrzik, PhD studend
Corinna Zogel, PhD


Peer-reviewed original publications

Nazlican H, Zeschnigk M, Claussen U, Michel S, Böhringer S, Gillessen-Kaesbach G, Buiting K, Horsthemke B (2004) Somatic mosaicism in patients with Angelman syndrome and an imprinting defect. Hum Mol Genet 13: 2547-55

Raca G, Buiting K, Das S (2004) Deletion Analysis of the Imprinting Center region in patients with Angelman syndrome and Prader-Willi syndrome. Genetic Testing 8: 387-394



Karin Buiting, PhD
Institut für Humangenetik, Universitätsklinikum
Hufelandstrasse 55
D-45122 Essen, Germany

Phone: +49 201 723 4555
Fax: +49 201 723 5900


Bernhard Horsthemke, PhD
Institut fuer Humangenetik
Universitaetsklinikum Essen
Hufelandstrasse 55
45122 Essen, Germany

Phone: +49 (201) 723 4556
Fax: +49 (201) 723 5900