Skip Navigation



Human Molecular Genetics Advance Access published online on August 27, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg291
© 2003 by Oxford University Press
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
12/20/2723    most recent
ddg291v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Horsthemke, B.
Right arrow Articles by Buiting, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Horsthemke, B.
Right arrow Articles by Buiting, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

©2003 Oxford University Press

Article

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 Horsthemke 1*, Hülya Nazlican 2, Johannes Hüsing 3, Ludger Klein-Hitpaß 4, Uwe Claussen 5, Susanne Michel 5, Christina Lich 2, Gabriele Gillessen-Kaesbach 2, and Karin Buiting 2

1 Institut für Humangenetik, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany
2 Institut für Humangenetik, Universitätsklinikum Essen, Germany
3 Institut für Medizinische Informatik, Biometrie und Epidemiologie, Universitätsklinikum Essen, Germany
4 Institut für Zellbiologie, Universitätsklinikum Essen, Germany
5 Institut für Humangenetik, Universität Jena

* To whom correspondence should be addressed. E-mail: b.horsthemke{at}uni-essen.de.


  Abstract

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 indicate 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.

One such gene may be SCG2, which encodes secretogranin II


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.