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Human Molecular Genetics Advance Access originally published online on August 27, 2003
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Human Molecular Genetics, 2003, Vol. 12, No. 20 2723-2732
DOI: 10.1093/hmg/ddg291
© 2003 Oxford University Press

Somatic mosaicism for maternal uniparental disomy 15 in a girl with Prader–Willi syndrome: confirmation by cell cloning and identification of candidate downstream genes

Bernhard Horsthemke1,*, Hülya Nazlican1, Johannes Hüsing2, Ludger Klein-Hitpaß3, Uwe Claussen4, Susanne Michel4, Christina Lich1, Gabriele Gillessen-Kaesbach1 and Karin Buiting1

1Institut für Humangenetik, 2Institut für Medizinische Informatik, Biometrie und Epidemiologie, and 3Institut für Zellbiologie, Universitätsklinikum Essen, Germany and 4Institut für Humangenetik, Universität Jena, Germany

Received July 8, 2003; Accepted August 15, 2003

Although uniparental disomy often results from the postzygotic rescue of a meiotic non-disjunction event, mosaicism is usually confined to the placenta. We describe a girl with Prader–Willi syndrome (PWS) who is mosaic for normal cells and cells with maternal uniparental disomy 15 [upd(15)mat] in blood and skin. Somatic mosaicism was confirmed by cloning and genotyping of skin fibroblasts. X inactivation studies indicated that upd occurred prior to X inactivation. RNA samples from the cloned cells were used in DNA microarray experiments to study the effect of upd(15)mat on the gene expression pattern of fibroblasts. Proof of principle was obtained by detecting several chromosome 15 genes known to be imprinted. We did not obtain any evidence for novel 15q genes showing imprinted expression in fibroblasts. Differentially expressed genes on other chromosomes are candidates for downstream genes regulated by an imprinted gene and may play a role in the pathogenesis of PWS. The finding of strongly reduced mRNA levels in upd(15)mat cells of the gene encoding secretogranin II (SCG2), which is a precursor of the dopamine releasing factor secretoneurin, raises the question whether hyperphagia in patients with PWS might be due to a defect in dopamine-modulated food reward circuits.

* To whom correspondence should be addressed at: Institut für Humangenetik, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany. Tel: +49 201-7234556; Fax: +49 201-7235900; Email: b.horsthemke{at}uni-essen.de


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