Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism

Nat Genet. 2013 Nov;45(11):1405-8. doi: 10.1038/ng.2776. Epub 2013 Sep 29.


Prader-Willi syndrome (PWS) is caused by the absence of paternally expressed, maternally silenced genes at 15q11-q13. We report four individuals with truncating mutations on the paternal allele of MAGEL2, a gene within the PWS domain. The first subject was ascertained by whole-genome sequencing analysis for PWS features. Three additional subjects were identified by reviewing the results of exome sequencing of 1,248 cases in a clinical laboratory. All four subjects had autism spectrum disorder (ASD), intellectual disability and a varying degree of clinical and behavioral features of PWS. These findings suggest that MAGEL2 is a new gene causing complex ASD and that MAGEL2 loss of function can contribute to several aspects of the PWS phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autistic Disorder / genetics*
  • Base Sequence
  • Child
  • Chromosomes, Human, Pair 15 / genetics
  • DNA Copy Number Variations
  • Female
  • Humans
  • Male
  • Prader-Willi Syndrome / genetics*
  • Proteins / genetics*
  • Sequence Analysis, DNA
  • Young Adult


  • MAGEL2 protein, human
  • Proteins