Abstract
Prader-Willi syndrome (PWS) is caused by deficiency for one or more paternally expressed imprinted transcripts within chromosome 15q11-q13, including SNURF-SNRPN and multiple small nucleolar RNAs (snoRNAs). Balanced chromosomal translocations that preserve expression of SNURF-SNRPN and centromeric genes but separate the snoRNA HBII-85 cluster from its promoter cause PWS. A microdeletion of the HBII-85 snoRNAs in a child with PWS provides, in combination with previous data, effectively conclusive evidence that deficiency of HBII-85 snoRNAs causes the key characteristics of the PWS phenotype, although some atypical features suggest that other genes in the region may make more subtle phenotypic contributions.
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Acknowledgements
This work was supported by US National Institutes of Health grants HD-037283 and M01-RR00188 (General Clinical Research Center), HD-024064 (Mental Retardation and Developmental Disabilities Research Center) and RR-019478 (Rare Disease Clinical Research Consortia). We thank J. Bressler for critical reading of the manuscript.
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Sahoo, T., del Gaudio, D., German, J. et al. Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nat Genet 40, 719–721 (2008). https://doi.org/10.1038/ng.158
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DOI: https://doi.org/10.1038/ng.158
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