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. 1995 Feb;32(2):88–92. doi: 10.1136/jmg.32.2.88

DNA methylation based testing of 450 patients suspected of having Prader-Willi syndrome.

G Gillessen-Kaesbach 1, S Gross 1, S Kaya-Westerloh 1, E Passarge 1, B Horsthemke 1
PMCID: PMC1050225  PMID: 7760327

Abstract

Using a test based on parent of origin specific DNA methylation at the D15S63 (PW71) locus, we studied 385 patients (aged 1 to 36 years) for diagnostic confirmation of Prader-Willi syndrome (PWS) and 65 infants (aged 0 to 12 months) with severe hypotonia of unknown cause. Fifty eight of 385 patients were examined personally; 28/58 patients had PWS and lacked the paternal PW71 band and 30/58 patients, who did not have PWS, had a normal methylation pattern. In five of these patients, a differential diagnosis was made (Ohdo-like blepharophimosis syndrome, Alstrøm syndrome, Cohen syndrome, Bardet-Biedl syndrome, and pseudohypoparathyroidism). A total of 327/385 blood samples was sent to us from outside. The test confirmed the diagnosis of PWS in 112/327 patients. Most of the other 215 patients lacked the major diagnostic criteria such as neonatal hypotonia, feeding problems, characteristic facies, and hypogenitalism. On the other hand, 29/65 hypotonic infants tested positive for PWS. We conclude that the PW71 methylation test detects most, if not all, patients with typical PWS and that PWS is often not recognised in infants and wrongly suspected in obese and mentally retarded patients.

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Selected References

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  1. Buiting K., Dittrich B., Robinson W. P., Guitart M., Abeliovich D., Lerer I., Horsthemke B. Detection of aberrant DNA methylation in unique Prader-Willi syndrome patients and its diagnostic implications. Hum Mol Genet. 1994 Jun;3(6):893–895. doi: 10.1093/hmg/3.6.893. [DOI] [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. Clayton-Smith J., Krajewska-Walasek M., Fryer A., Donnai D. Ohdo-like blepharophimosis syndrome with distinctive facies, neonatal hypotonia, mental retardation and hypoplastic teeth. Clin Dysmorphol. 1994 Apr;3(2):115–120. [PubMed] [Google Scholar]
  4. Dittrich B., Buiting K., Gross S., Horsthemke B. Characterization of a methylation imprint in the Prader-Willi syndrome chromosome region. Hum Mol Genet. 1993 Dec;2(12):1995–1999. doi: 10.1093/hmg/2.12.1995. [DOI] [PubMed] [Google Scholar]
  5. Dittrich B., Robinson W. P., Knoblauch H., Buiting K., Schmidt K., Gillessen-Kaesbach G., Horsthemke B. Molecular diagnosis of the Prader-Willi and Angelman syndromes by detection of parent-of-origin specific DNA methylation in 15q11-13. Hum Genet. 1992 Nov;90(3):313–315. doi: 10.1007/BF00220089. [DOI] [PubMed] [Google Scholar]
  6. Driscoll D. J., Waters M. F., Williams C. A., Zori R. T., Glenn C. C., Avidano K. M., Nicholls R. D. A DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader-Willi syndromes. Genomics. 1992 Aug;13(4):917–924. doi: 10.1016/0888-7543(92)90001-9. [DOI] [PubMed] [Google Scholar]
  7. Glenn C. C., Porter K. A., Jong M. T., Nicholls R. D., Driscoll D. J. Functional imprinting and epigenetic modification of the human SNRPN gene. Hum Mol Genet. 1993 Dec;2(12):2001–2005. doi: 10.1093/hmg/2.12.2001. [DOI] [PubMed] [Google Scholar]
  8. Holm V. A., Cassidy S. B., Butler M. G., Hanchett J. M., Greenswag L. R., Whitman B. Y., Greenberg F. Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics. 1993 Feb;91(2):398–402. [PMC free article] [PubMed] [Google Scholar]
  9. Lerer I., Meiner V., Pashut-Lavon I., Abeliovich D. Molecular diagnosis of Prader-Willi syndrome: parent-of-origin dependent methylation sites and non-isotopic detection of (CA)n dinucleotide repeat polymorphisms. Am J Med Genet. 1994 Aug 1;52(1):79–84. doi: 10.1002/ajmg.1320520116. [DOI] [PubMed] [Google Scholar]
  10. Mascari M. J., Gottlieb W., Rogan P. K., Butler M. G., Waller D. A., Armour J. A., Jeffreys A. J., Ladda R. L., Nicholls R. D. The frequency of uniparental disomy in Prader-Willi syndrome. Implications for molecular diagnosis. N Engl J Med. 1992 Jun 11;326(24):1599–1607. doi: 10.1056/NEJM199206113262404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Reis A., Dittrich B., Greger V., Buiting K., Lalande M., Gillessen-Kaesbach G., Anvret M., Horsthemke B. Imprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes. Am J Hum Genet. 1994 May;54(5):741–747. [PMC free article] [PubMed] [Google Scholar]

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