Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism

• Published in: Nature genetics Vol. 45; no. 11; pp. 1405 - 1408
• Main Authors: Schaaf, Christian P, Gonzalez-Garay, Manuel L, Xia, Fan, Potocki, Lorraine, Gripp, Karen W, Zhang, Baili, Peters, Brock A, McElwain, Mark A, Drmanac, Radoje, Beaudet, Arthur L, Caskey, C Thomas, Yang, Yaping
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2013; Nature Publishing Group
• Subjects: 692/308/2056; 692/699/476/1373; Adolescent; Agriculture; Animal Genetics and Genomics; Autism; Autistic Disorder - genetics; Base Sequence; Behavior; Biomedicine; Cancer Research; Charitable foundations; Child; Chromosomes; Chromosomes, Human, Pair 15 - genetics; DNA Copy Number Variations; Exome sequencing; Female; Gene Function; Gene mutations; Genes; Genetic aspects; Genomes; Genomics; Genotype & phenotype; Human Genetics; Humans; Identification and classification; letter; Male; Methods; Mutation; Prader-Willi syndrome; Prader-Willi Syndrome - genetics; Proteins; Proteins - genetics; Sequence Analysis, DNA; Studies; Young Adult
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2776

Christian Schaaf, Manuel Gonzalez-Garay and colleagues report the identification of four individuals with truncating mutations on the paternal allele of MAGEL2 , a gene within the imprinted domain linked to Prader-Willi syndrome (PWS). The four individuals have PWS or PWS-related phenotypes, and all have autism. 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.