Imprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes

Am J Hum Genet. 1994 May;54(5):741-7.


The D15S9 and D15S63 loci in the Prader-Willi/Angelman syndrome region on chromosome 15 are subject to parent-of-origin-specific DNA methylation. We have found two Prader-Willi syndrome families in which the patients carry a maternal methylation imprint on the paternal chromosome. In one of these families, the patients have a small deletion encompassing the gene for the small nuclear ribonucleoprotein polypeptide N, which maps 130 kb telomeric to D15S63. Furthermore, we have identified a pair of nondeletion Angelman syndrome sibs and two isolated Angelman syndrome patients who carry a paternal methylation imprint on the maternal chromosome. These Angelman and Prader-Willi syndrome patients may have a defect in the imprinting process in 15q11-13. We propose a model in which a cis-acting mutation prevents the resetting of the imprinting signal in the germ line and thus disturbs the expression of imprinted genes in this region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelman Syndrome / genetics*
  • Blotting, Southern
  • Chromosome Mapping
  • Chromosomes, Human, Pair 15*
  • DNA / analysis*
  • DNA / genetics
  • DNA / metabolism
  • Female
  • Genetic Markers
  • Genotype
  • Humans
  • Male
  • Methylation
  • Models, Genetic
  • Mutation*
  • Prader-Willi Syndrome / genetics*
  • Restriction Mapping


  • Genetic Markers
  • DNA