De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch

Nat Genet. 2000 May;25(1):74-8. doi: 10.1038/75629.


Prader-Willi syndrome (PWS) is a neurogenetic disease characterized by infantile hypotonia, gonadal hypoplasia, obsessive behaviour and neonatal feeding difficulties followed by hyperphagia, leading to profound obesity. PWS is due to a lack of paternal genetic information at 15q11-q13 (ref. 2). Five imprinted, paternally expressed genes map to the PWS region, MKRN3 (ref. 3), NDN (ref. 4), NDNL1 (ref. 5), SNRPN (refs 6-8 ) and IPW (ref. 9), as well as two poorly characterized framents designated PAR-1 and PAR-5 (ref. 10). Imprinting of this region involves a bipartite 'imprinting centre' (IC), which overlaps SNRPN (refs 10,11). Deletion of the SNRPN promoter/exon 1 region (the PWS IC element) appears to impair the establishment of the paternal imprint in the male germ line and leads to PWS. Here we report a PWS family in which the father is mosaic for an IC deletion on his paternal chromosome. The deletion chromosome has acquired a maternal methylation imprint in his somatic cells. We have made identical findings in chimaeric mice generated from two independent embryonic stem (ES) cell lines harbouring a similar deletion. Our studies demonstrate that the PWS IC element is not only required for the establishment of the paternal imprint, but also for its postzygotic maintenance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Autoantigens / genetics*
  • Autoantigens / metabolism
  • Blotting, Southern
  • Cell Line
  • Child, Preschool
  • DNA Methylation
  • Embryo, Mammalian / physiology*
  • Exons / genetics*
  • Female
  • Genomic Imprinting / genetics*
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Pedigree
  • Prader-Willi Syndrome / genetics
  • Ribonucleoproteins, Small Nuclear / genetics*
  • Sequence Deletion*
  • snRNP Core Proteins


  • Autoantigens
  • Ribonucleoproteins, Small Nuclear
  • SNRPN protein, human
  • snRNP Core Proteins