Human Molecular Genetics, 1999, Vol. 8, No. 10 1867-1873
© 1999 Oxford University Press
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Towards a molecular understandingof Prader–Willi and Angelman syndromes
Howard Hughes Medical Institute and Department of Cell andDevelopmental Biology, University of Pennsylvania School of Medicine,Philadelphia, PA 19104, USA
ABSTRACT
Prader–Willi syndrome (PWS) and Angelman syndrome(AS) are two distinct neurological disorders that map to human chromosome15q11–q13 and involve perturbations of imprinted gene expression.PWS is caused by a deficiency of paternal gene expression and ASis caused by a deficiency of maternal gene expression. Experimentsin the last year have focused on molecular analysis of the humanchromosomal region as well as the homologous region on central mousechromosome 7. New transcripts and exons have been identified andthe epigenetic status of the PWS/AS region in mice andhumans has been examined. The imprinting center that is hypothesizedto control the switch between the maternal and paternal epigenotypeshas also been characterized in greater detail and a mouse modelthat deletes the homologous element demonstrates a conservationin imprinting center function between mice and humans. In addition,analysis of non-deletion AS patients has revealed that UBE3A intragenicmutations are found in a significant number of cases. However, bothhuman patients and mouse model systems indicate that other genesmay also contribute to the AS phenotype. Thus, although much hasbeen learned in the last year, considerable information is stillrequired before these complex syndromes are fully understood.
FOOTNOTES
a To whom correspondenceshould be addressed. Tel: +1 215 898 9063; Fax: +1215 573 6434; Email: bartolom{at}mail.med.upenn.edu
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