Epimutations in Prader-Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect

Am J Hum Genet. 2003 Mar;72(3):571-7. doi: 10.1086/367926. Epub 2003 Jan 23.


Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurogenetic disorders that are caused by the loss of function of imprinted genes in 15q11-q13. In a small group of patients, the disease is due to aberrant imprinting and gene silencing. Here, we describe the molecular analysis of 51 patients with PWS and 85 patients with AS who have such a defect. Seven patients with PWS (14%) and eight patients with AS (9%) were found to have an imprinting center (IC) deletion. Sequence analysis of 32 patients with PWS and no IC deletion and 66 patients with AS and no IC deletion did not reveal any point mutation in the critical IC elements. The presence of a faint methylated band in 27% of patients with AS and no IC deletion suggests that these patients are mosaic for an imprinting defect that occurred after fertilization. In patients with AS, the imprinting defect occurred on the chromosome that was inherited from either the maternal grandfather or grandmother; however, in all informative patients with PWS and no IC deletion, the imprinting defect occurred on the chromosome inherited from the paternal grandmother. These data suggest that this imprinting defect results from a failure to erase the maternal imprint during spermatogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelman Syndrome / genetics*
  • Base Sequence
  • Chromosome Aberrations*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 15*
  • DNA Primers
  • Genomic Imprinting*
  • Humans
  • Microsatellite Repeats
  • Molecular Sequence Data
  • Mutation*
  • Point Mutation*
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide*
  • Prader-Willi Syndrome / genetics*
  • Sequence Deletion


  • DNA Primers

Associated data

  • GENBANK/AC009696
  • GENBANK/AF143819
  • OMIM/105830