Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and 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.
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].
Christian P
CP
Schaaf
Manuel L
ML
Gonzalez-Garay
Fan
F
Xia
Lorraine
L
Potocki
Karen W
KW
Gripp
Baili
B
Zhang
Brock A
BA
Peters
Mark A
MA
McElwain
Radoje
R
Drmanac
Arthur L
AL
Beaudet
C Thomas
CT
Caskey
Yaping
Y
Yang
D000293:Adolescent; D001321:Autistic Disorder / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins
D011506:Proteins; C510822:MAGEL2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins