Molecular characterization of two proximal deletion breakpoint regions in both Prader-Willi and Angelman syndrome patients

Am J Hum Genet. 1995 Jul;57(1):40-8.


Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation syndromes caused by paternal and maternal deficiencies, respectively, in chromosome 15q11-q13. Approximately 70% of these patients have a large deletion of approximately 4 Mb extending from D15S9 (ML34) through D15S12 (IR10). To further characterize the deletion breakpoints proximal to D15S9, three new polymorphic microsatellite markers were developed that showed observed heterozygosities of 60%-87%. D15S541 and D15S542 were isolated from YAC A124A3 containing the D15S18 (IR39) locus. D15S543 was isolated from a cosmid cloned from the proximal right end of YAC 254B5 containing the D15S9 (ML34) locus. Gene-centromere mapping of these markers, using a panel of ovarian teratomas of known meiotic origin, extended the genetic map of chromosome 15 by 2-3 cM toward the centromere. Analysis of the more proximal S541/S542 markers on 53 Prader-Willi and 33 Angelman deletion patients indicated two classes of patients: 44% (35/80) of the informative patients were deleted for these markers (class I), while 56% (45/80) were not deleted (class II), with no difference between PWS and AS. In contrast, D15S543 was deleted in all informative patients (13/48) or showed the presence of a single allele (in 35/48 patients), suggesting that this marker is deleted in the majority of PWS and AS cases. These results confirm the presence of two common proximal deletion breakpoint regions in both Prader-Willi and Angelman syndromes and are consistent with the same deletion mechanism being responsible for paternal and maternal deletions. One breakpoint region lies between D15S541/S542 and D15S543, with an additional breakpoint region being proximal to D15S541/S542.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelman Syndrome / genetics*
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 15 / genetics*
  • DNA, Satellite / analysis
  • Female
  • Genetic Markers
  • Humans
  • Lod Score
  • Molecular Sequence Data
  • Ovarian Neoplasms / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Prader-Willi Syndrome / genetics*
  • Sequence Deletion*
  • Teratoma / genetics


  • DNA, Satellite
  • Genetic Markers