Abstract
The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are distinct genetic disorders that are caused by a deletion of chromosome region 15q11-13 or by uniparental disomy for chromosome 15. Whereas PWS results from the absence of a paternal copy of 15q11-13, the absence of a maternal copy of 15q11-13 leads to AS. We have found that an MspI/HpaII restriction site at the D15S63 locus in 15q11-13 is methylated on the maternally derived chromosome, but unmethylated on the paternally derived chromosome. Based on this difference, we have devised a rapid diagnostic test for patients suspected of having PWS and AS.
References
Buiting K, Neumann M, Lüdecke HJ, Senger G, Claussen U, Antich J, Passarge E, Hotsthemke B (1990) Microdissection of the Prader-Willi syndrome chromosome region and identification of potential gene sequences. Genomics 6:521–527
Buiting K, Greger V, Brownstein BH, Mohr RM, Voiculescu I, Winterpacht A, Zabel B, Horsthemke B (1992) A putative gene family in 15q11–13 and 16p11.2: possible implications for Prader-Willi and Agelman syndromes. Proc Natl Acad Sci USA 89:5457–5461
Driscoll DJ, Waters MF, Williams CA, Zori RT, Glenn CC, Avidano KM, Nicholls RD (1992) DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader-Willi syndromes. Genomics 13:917–924
Knoll JHM, Nicholls RD, Magenis RE, Graham JM Jr, Lalande M, Latt SA (1989) Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. Am J Med Genet 32:285–290
Ledbetter DH, Riccardi VM, Airhart SD, Strobel RJ, Keenan BS, Crawford JD (1981) Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. N Engl J Med 304:325–329
Malcolm S, Clayton-Smith J, Nicholls M, Robb S, Webb T, Armour JAL, Jeffreys AJ, Pembrey ME (1991) Uniparental paternal disomy in Angelman's syndrome. Lancet 337:694–697
Nicholls RD, Knoll JHM, Butler MG, Karam S, Lalande M (1989) Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willi syndrome. Nature 342:281–285
Pembrey M, Fennell SJ, Van Den Berghe J, Fitchett M, Summers D, Butler L, Clarke C, Griffiths M, Thompson E, Super M, Baraitser M (1989) The association of Angelman's syndrome with deletions within 15q11–13. J Med Genet 26:73–77
Robinson W, Bottani A, Yagang X, Balakrishman J, Binkert F, Mächler M, Prader A, Schinzel A (1991) Molecular, cytogenetic, and clinical investigations of Prader-Willi syndrome patients. Am J Hum Genet 49:1219–1234
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dittrich, B., Robinson, W.P., Knoblauch, H. et al. Molecular diagnosis of the Prader-Willi and Angelman syndromes by detection of parent-of-origin specific DNA methylation in 15q11-13. Hum Genet 90, 313–315 (1992). https://doi.org/10.1007/BF00220089
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00220089