Towards a molecular understanding of Prader-Willi and Angelman syndromes.
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct neurological disorders that map to human chromosome 15q11-q13 and involve perturbations of imprinted gene expression. PWS is caused by a deficiency of paternal gene expression and AS is caused by a deficiency of maternal gene expression. Experiments in the last year have focused on molecular analysis of the human chromosomal region as well as the homologous region on central mouse chromosome 7. New transcripts and exons have been identified and the epigenetic status of the PWS/AS region in mice and humans has been examined. The imprinting center that is hypothesized to control the switch between the maternal and paternal epigenotypes has also been characterized in greater detail and a mouse model that deletes the homologous element demonstrates a conservation in imprinting center function between mice and humans. In addition, analysis of non-deletion AS patients has revealed that UBE3A intragenic mutations are found in a significant number of cases. However, both human patients and mouse model systems indicate that other genes may also contribute to the AS phenotype. Thus, although much has been learned in the last year, considerable information is still required before these complex syndromes are fully understood.
Mann
M R
MR
Howard Hughes Medical Institute and Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Bartolomei
M S
MS
D017204:Angelman Syndrome / Q000235:genetics*; D000818:Animals; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004195:Disease Models, Animal; D005796:Genes / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics; D006801:Humans; D051379:Mice; D011218:Prader-Willi Syndrome / Q000235:genetics*