Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism

  • Nat Genet. 2013 Nov;45(11):1405-8. doi: 10.1038/ng.2776.
Christian P Schaaf  1 ,  Manuel L Gonzalez-Garay ,  Fan Xia ,  Lorraine Potocki ,  Karen W Gripp ,  Baili Zhang ,  Brock A Peters ,  Mark A McElwain ,  Radoje Drmanac ,  Arthur L Beaudet ,  C Thomas Caskey ,  Yaping Yang
Affiliations
  • 1. 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. [2] Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, USA. [3].
PMID: 24076603 DOI: 10.1038/ng.2776
Abstract

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.