Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1990 Jul;47(1):149–155.

Angelman syndrome: three molecular classes identified with chromosome 15q11q13-specific DNA markers.

J H Knoll 1, R D Nicholls 1, R E Magenis 1, K Glatt 1, J M Graham Jr 1, L Kaplan 1, M Lalande 1
PMCID: PMC1683759  PMID: 1971993

Abstract

Angelman syndrome (AS) and Prader-Willi syndrome (PWS) share a cytogenetic deletion of chromosome 15q11q13. To determine the extent of deletion in AS we analyzed the DNA of 19 AS patients, including two sib pairs, with the following chromosome 15q11q13--specific DNA markers: D15S9-D15S13, D15S17, D15S18, and D15S24. Three molecular classes were identified. Class I showed a deletion of D15S9-D15S13 and D15S18; class II showed a deletion of D15S9-D15S13; and in class III, including both sib pairs, no deletion was detected. These molecular classes appear to be identical to those observed in PWS. High-resolution cytogenetic data were available on 16 of the patients, and complete concordance between the presence of a cytogenetic deletion and a molecular deletion was observed. No submicroscopic deletions were detected. DNA samples from the parents of 10 patients with either a class I or a class II deletion were available for study. In seven of the 10 families, RFLPs were informative as to the parental origin of the deletion. In all informative families, the deleted chromosome 15 was observed to be of maternal origin. This finding is in contrast to the paternal origin of the deletions in PWS and is currently the only molecular difference observed between the two syndromes.

Full text

PDF
149

Images in this article

151Figure 2
on p.151
151Figure 3
on p.151
152Figure 4
on p.152
152Figure 5
on p.152

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aldridge J., Kunkel L., Bruns G., Tantravahi U., Lalande M., Brewster T., Moreau E., Wilson M., Bromley W., Roderick T. A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet. 1984 May;36(3):546–564. [PMC free article] [PubMed] [Google Scholar]
  2. Butler M. G., Meaney F. J., Palmer C. G. Clinical and cytogenetic survey of 39 individuals with Prader-Labhart-Willi syndrome. Am J Med Genet. 1986 Mar;23(3):793–809. doi: 10.1002/ajmg.1320230307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Butler M. G., Palmer C. G. Parental origin of chromosome 15 deletion in Prader-Willi syndrome. Lancet. 1983 Jun 4;1(8336):1285–1286. doi: 10.1016/s0140-6736(83)92745-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cooke A., Tolmie J. L., Glencross F. J., Boyd E., Clarke M. M., Day R., Stephenson J. B., Connor J. M. Detection of a 15q deletion in a child with Angelman syndrome by cytogenetic analysis and flow cytometry. Am J Med Genet. 1989 Apr;32(4):545–549. doi: 10.1002/ajmg.1320320424. [DOI] [PubMed] [Google Scholar]
  5. Donlon T. A., Lalande M., Wyman A., Bruns G., Latt S. A. Isolation of molecular probes associated with the chromosome 15 instability in the Prader-Willi syndrome. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4408–4412. doi: 10.1073/pnas.83.12.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Donlon T. A. Similar molecular deletions on chromosome 15q11.2 are encountered in both the Prader-Willi and Angelman syndromes. Hum Genet. 1988 Dec;80(4):322–328. doi: 10.1007/BF00273644. [DOI] [PubMed] [Google Scholar]
  7. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  8. Francke U., Holmes L. B., Atkins L., Riccardi V. M. Aniridia-Wilms' tumor association: evidence for specific deletion of 11p13. Cytogenet Cell Genet. 1979;24(3):185–192. doi: 10.1159/000131375. [DOI] [PubMed] [Google Scholar]
  9. Grundy P., Koufos A., Morgan K., Li F. P., Meadows A. T., Cavenee W. K. Familial predisposition to Wilms' tumour does not map to the short arm of chromosome 11. Nature. 1988 Nov 24;336(6197):374–376. doi: 10.1038/336374a0. [DOI] [PubMed] [Google Scholar]
  10. Huff V., Compton D. A., Chao L. Y., Strong L. C., Geiser C. F., Saunders G. F. Lack of linkage of familial Wilms' tumour to chromosomal band 11p13. Nature. 1988 Nov 24;336(6197):377–378. doi: 10.1038/336377a0. [DOI] [PubMed] [Google Scholar]
  11. Kaplan L. C., Wharton R., Elias E., Mandell F., Donlon T., Latt S. A. Clinical heterogeneity associated with deletions in the long arm of chromosome 15: report of 3 new cases and their possible genetic significance. Am J Med Genet. 1987 Sep;28(1):45–53. doi: 10.1002/ajmg.1320280107. [DOI] [PubMed] [Google Scholar]
  12. Knoll J. H., Nicholls R. D., Lalande M. On the parental origin of the deletion in Angelman syndrome. Hum Genet. 1989 Sep;83(2):205–207. doi: 10.1007/BF00286723. [DOI] [PubMed] [Google Scholar]
  13. Knoll J. H., Nicholls R. D., Magenis R. E., Graham J. M., Jr, Lalande M., Latt S. A. Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. Am J Med Genet. 1989 Feb;32(2):285–290. doi: 10.1002/ajmg.1320320235. [DOI] [PubMed] [Google Scholar]
  14. Lalande M., Dryja T. P., Schreck R. R., Shipley J., Flint A., Latt S. A. Isolation of human chromosome 13-specific DNA sequences cloned from flow sorted chromosomes and potentially linked to the retinoblastoma locus. Cancer Genet Cytogenet. 1984 Dec;13(4):283–295. doi: 10.1016/0165-4608(84)90073-6. [DOI] [PubMed] [Google Scholar]
  15. Magenis R. E., Brown M. G., Lacy D. A., Budden S., LaFranchi S. Is Angelman syndrome an alternate result of del(15)(q11q13)? Am J Med Genet. 1987 Dec;28(4):829–838. doi: 10.1002/ajmg.1320280407. [DOI] [PubMed] [Google Scholar]
  16. Magenis R. E., Toth-Fejel S., Allen L. J., Black M., Brown M. G., Budden S., Cohen R., Friedman J. M., Kalousek D., Zonana J. Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: specific regions, extent of deletions, parental origin, and clinical consequences. Am J Med Genet. 1990 Mar;35(3):333–349. doi: 10.1002/ajmg.1320350307. [DOI] [PubMed] [Google Scholar]
  17. Mattei J. F., Mattei M. G., Giraud F. Prader-Willi syndrome and chromosome 15. A clinical discussion of 20 cases. Hum Genet. 1983;64(4):356–362. doi: 10.1007/BF00292367. [DOI] [PubMed] [Google Scholar]
  18. Nicholls R. D., Knoll J. H., Butler M. G., Karam S., Lalande M. Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature. 1989 Nov 16;342(6247):281–285. doi: 10.1038/342281a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nicholls R. D., Knoll J. H., Glatt K., Hersh J. H., Brewster T. D., Graham J. M., Jr, Wurster-Hill D., Wharton R., Latt S. A. Restriction fragment length polymorphisms within proximal 15q and their use in molecular cytogenetics and the Prader-Willi syndrome. Am J Med Genet. 1989 May;33(1):66–77. doi: 10.1002/ajmg.1320330109. [DOI] [PubMed] [Google Scholar]
  20. Niikawa N., Ishikiriyama S. Clinical and cytogenetic studies of the Prader-Willi syndrome: evidence of phenotype-karyotype correlation. Hum Genet. 1985;69(1):22–27. doi: 10.1007/BF00295524. [DOI] [PubMed] [Google Scholar]
  21. Pashayan H. M., Singer W., Bove C., Eisenberg E., Seto B. The Angelman syndrome in two brothers. Am J Med Genet. 1982 Nov;13(3):295–298. doi: 10.1002/ajmg.1320130311. [DOI] [PubMed] [Google Scholar]
  22. Pembrey M., Fennell S. J., van den Berghe J., Fitchett M., Summers D., Butler L., Clarke C., Griffiths M., Thompson E., Super M. The association of Angelman's syndrome with deletions within 15q11-13. J Med Genet. 1989 Feb;26(2):73–77. doi: 10.1136/jmg.26.2.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rich D. C., Witkowski C. M., Summers K. M., van Tuinen P., Ledbetter D. H. Highly polymorphic locus D15S24 (CMW-1) maps to 15pter-q13. [HGM9 provisional no. D15S24]. Nucleic Acids Res. 1988 Sep 12;16(17):8740–8740. doi: 10.1093/nar/16.17.8740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Seabright M. A rapid banding technique for human chromosomes. Lancet. 1971 Oct 30;2(7731):971–972. doi: 10.1016/s0140-6736(71)90287-x. [DOI] [PubMed] [Google Scholar]
  25. Tantravahi U., Nicholls R. D., Stroh H., Ringer S., Neve R. L., Kaplan L., Wharton R., Wurster-Hill D., Graham J. M., Jr, Cantú E. S. Quantitative calibration and use of DNA probes for investigating chromosome abnormalities in the Prader-Willi syndrome. Am J Med Genet. 1989 May;33(1):78–87. doi: 10.1002/ajmg.1320330110. [DOI] [PubMed] [Google Scholar]
  26. Williams C. A., Gray B. A., Hendrickson J. E., Stone J. W., Cantú E. S. Incidence of 15q deletions in the Angelman syndrome: a survey of twelve affected persons. Am J Med Genet. 1989 Mar;32(3):339–345. doi: 10.1002/ajmg.1320320313. [DOI] [PubMed] [Google Scholar]
  27. Yunis J. J. High resolution of human chromosomes. Science. 1976 Mar 26;191(4233):1268–1270. doi: 10.1126/science.1257746. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES