Search tips
Search criteria 


Logo of jmedgeneJournal of Medical GeneticsVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
J Med Genet. 1993 September; 30(9): 756–760.
PMCID: PMC1016533

Uniparental disomy explains the occurrence of the Angelman or Prader-Willi syndrome in patients with an additional small inv dup(15) chromosome.


A patient with Angelman syndrome and a 46,XY/47,XY,+inv dup(15)(pter-->q11: q11-->pter) karyotype and a patient with Prader-Willi syndrome and a 46,XY/47,XY,+inv dup(15)(pter-->q12: q12-->pter) karyotype were investigated with molecular markers along chromosome 15. Paternal uniparental isodisomy was found for all informative markers in the first case which indicates that this, rather than the presence of the extra chromosome, is the cause of the Angelman syndrome phenotype. Similarly, the PWS patient showed maternal uniparental distomy with absence of PWS region material on the inv dup(15) chromosome. If (1) marker chromosomes are an occasional by product of 'rescuing' a trisomic fertilisation, or (2) if duplication of the normal homologue in a zygote which has inherited a marker in place of the normal corresponding chromosome 'rescues' an aneuploid fertilisation, or (3) if the presence or formation of a marker chromosome increases the probability of non-disjunction, then uniparental disomy might be found occasionally in other subjects with de novo marker chromosomes.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Knoll JH, Nicholls RD, Magenis RE, Graham JM, Jr, Lalande M, Latt SA. 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. [PubMed]
  • Malcolm S, Clayton-Smith J, Nichols M, Robb S, Webb T, Armour JA, Jeffreys AJ, Pembrey ME. Uniparental paternal disomy in Angelman's syndrome. Lancet. 1991 Mar 23;337(8743):694–697. [PubMed]
  • Nicholls RD, Pai GS, Gottlieb W, Cantú ES. Paternal uniparental disomy of chromosome 15 in a child with Angelman syndrome. Ann Neurol. 1992 Oct;32(4):512–518. [PubMed]
  • Mutirangura A, Greenberg F, Butler MG, Malcolm S, Nicholls RD, Chakravarti A, Ledbetter DH. Multiplex PCR of three dinucleotide repeats in the Prader-Willi/Angelman critical region (15q11-q13): molecular diagnosis and mechanism of uniparental disomy. Hum Mol Genet. 1993 Feb;2(2):143–151. [PubMed]
  • Nicholls RD, Knoll JH, Butler MG, Karam S, Lalande M. Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature. 1989 Nov 16;342(6247):281–285. [PubMed]
  • Robinson WP, Bottani A, Xie YG, Balakrishman J, Binkert F, Mächler M, Prader A, Schinzel A. Molecular, cytogenetic, and clinical investigations of Prader-Willi syndrome patients. Am J Hum Genet. 1991 Dec;49(6):1219–1234. [PubMed]
  • Mascari MJ, Gottlieb W, Rogan PK, Butler MG, Waller DA, Armour JA, Jeffreys AJ, Ladda RL, Nicholls RD. The frequency of uniparental disomy in Prader-Willi syndrome. Implications for molecular diagnosis. N Engl J Med. 1992 Jun 11;326(24):1599–1607. [PubMed]
  • Ridler MA, Garrod O, Berg JM. A case of Prader-Willi syndrome in a girl with a small extra chromosome. Acta Paediatr Scand. 1971 Mar;60(2):222–226. [PubMed]
  • Michaelsen KF, Lundsteen C, Hansen FJ. Prader-Willi syndrome and chromosomal mosaicism 46,XY/47,XY,+mar in two cases. Clin Genet. 1979 Sep;16(3):147–150. [PubMed]
  • Fujita H, Sakamoto Y, Hamamoto Y. An extra idic(15p)(q11) chromosome in Prader-Willi syndrome. Hum Genet. 1980;55(3):409–411. [PubMed]
  • Wisniewski LP, Witt ME, Ginsberg-Fellner F, Wilner J, Desnick RJ. Prader-Willi syndrome and a bisatellited derivative of chromosome 15. Clin Genet. 1980 Jul;18(1):42–47. [PubMed]
  • Ledbetter DH, Mascarello JT, Riccardi VM, Harper VD, Airhart SD, Strobel RJ. Chromosome 15 abnormalities and the Prader-Willi syndrome: a follow-up report of 40 cases. Am J Hum Genet. 1982 Mar;34(2):278–285. [PubMed]
  • Wulfsberg EA, Sparkes RS, Klisak IJ, Gurfield WB. A 15 leads to 1 translocation in a patient mosaic for presence or absence of an isodic(15p)(q11). Am J Med Genet. 1982 Dec;13(4):417–421. [PubMed]
  • Mattei JF, Mattei MG, Giraud F. Prader-Willi syndrome and chromosome 15. A clinical discussion of 20 cases. Hum Genet. 1983;64(4):356–362. [PubMed]
  • Robinson WP, Binkert F, Giné R, Vazquez C, Müller W, Rosenkranz W, Schinzel A. Clinical and molecular analysis of five inv dup(15) patients. Eur J Hum Genet. 1993;1(1):37–50. [PubMed]
  • Purvis-Smith SG, Saville T, Manass S, Yip MY, Lam-Po-Tang PR, Duffy B, Johnston H, Leigh D, McDonald B. Uniparental disomy 15 resulting from "correction" of an initial trisomy 15. Am J Hum Genet. 1992 Jun;50(6):1348–1350. [PubMed]
  • Cassidy SB, Lai LW, Erickson RP, Magnuson L, Thomas E, Gendron R, Herrmann J. Trisomy 15 with loss of the paternal 15 as a cause of Prader-Willi syndrome due to maternal disomy. Am J Hum Genet. 1992 Oct;51(4):701–708. [PubMed]
  • Donlon TA, Lalande M, Wyman A, Bruns G, Latt SA. 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. [PubMed]
  • Tantravahi U, Nicholls RD, Stroh H, Ringer S, Neve RL, Kaplan L, Wharton R, Wurster-Hill D, Graham JM, Jr, Cantú ES, et al. 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. [PubMed]
  • Nicholls RD, Knoll JH, Glatt K, Hersh JH, Brewster TD, Graham JM, Jr, Wurster-Hill D, Wharton R, Latt SA. 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. [PubMed]
  • Rich DC, Witkowski CM, Summers KM, van Tuinen P, Ledbetter DH. Highly polymorphic locus D15S24 (CMW-1) maps to 15pter-q13. [HGM9 provisional no. D15S24]. Nucleic Acids Res. 1988 Sep 12;16(17):8740–8740. [PMC free article] [PubMed]
  • Armour JA, Povey S, Jeremiah S, Jeffreys AJ. Systematic cloning of human minisatellites from ordered array charomid libraries. Genomics. 1990 Nov;8(3):501–512. [PubMed]
  • Mutirangura A, Kuwano A, Ledbetter SA, Chinault AC, Ledbetter DH. Dinucleotide repeat polymorphism at the D15S11 locus in the Angelman/Prader-Willi region (AS/PWS) of chromosome 15. Hum Mol Genet. 1992 May;1(2):139–139. [PubMed]
  • Mutirangura A, Ledbetter SA, Kuwano A, Chinault AC, Ledbetter DH. Dinucleotide repeat polymorphism at the GABAA receptor beta 3 (GABRB3) locus in the Angelman/Prader-Willi region (AS/PWS) of chromosome 15. Hum Mol Genet. 1992 Apr;1(1):67–67. [PubMed]
  • Glatt KA, Sinnett D, Lalande M. Dinucleotide repeat polymorphism at the GABAA receptor alpha 5 (GABRA5) locus at chromosome 15q11-q13. Hum Mol Genet. 1992 Aug;1(5):348–348. [PubMed]
  • Kuwano A, Mutirangura A, Dittrich B, Buiting K, Horsthemke B, Saitoh S, Niikawa N, Ledbetter SA, Greenberg F, Chinault AC, et al. Molecular dissection of the Prader-Willi/Angelman syndrome region (15q11-13) by YAC cloning and FISH analysis. Hum Mol Genet. 1992 Sep;1(6):417–425. [PubMed]
  • Robinson WP, Spiegel R, Schinzel AA. Deletion breakpoints associated with the Prader-Willi and Angelman syndromes (15q11-q13) are not sites of high homologous recombination. Hum Genet. 1993 Mar;91(2):181–184. [PubMed]
  • Dittrich B, Robinson WP, 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. [PubMed]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group