Prader-Willi syndrome (PWS) is a genetically and clinically complex disorder. From a molecular standpoint, a major question has been the contribution of individual genes within the Prader-Willi domain on chromosome 15 to the overall clinical phenotype. Many animal models have attempted to address this question, but have not been able to fully recapitulate the human phenotypes. Individuals with point mutations in MAGEL2, one of the genes within the Prader-Willi domain, provide a unique opportunity to understand this gene’s contribution in an actual human context.
We propose to investigate the behavioral, cognitive, and endocrinological phenotypes of ten individuals with point mutations in the MAGEL2 gene. Respective individuals will be evaluated by a team of expert psychologists and geneticists at Texas Children’s Hospital. They will be assessed for cognitive and intellectual deficits, autism spectrum disorder, social responsiveness, other behavioral features, growth hormone deficiency, puberty and sexual development, thyroid function, lipids, hormones related to hunger and eating, bone mineral density, body composition, and scoliosis. Findings will be compared side-by-side to those of individuals with classic Prader-Willi syndrome.
This study will allow to determine the specific manifestations caused by a single gene within the Prader-Willi domain, which will shed light into the overall molecular causes and contributions of individual genes to Prader-Willi syndrome. It will allow narrowing down targets and outcome measures that could be considered in clinical trials for PWS, as they relate to specific genes and pathways.
Schaaf-Yang syndrome overview: Report of 78 individuals. McCarthy J, Lupo PJ, Kovar E, Rech M, Bostwick B, Scott D, Kraft K, Roscioli T, Charrow J, Schrier Vergano SA, Lose E, Smiegel R, Lacassie Y, Schaaf CP. American Journal of Medical Genetics Part A. 2018 Oct 10.
Hormonal, metabolic and skeletal phenotype of Schaaf-Yang syndrome: a comparison to Prader-Willi syndrome. McCarthy JM, McCann-Crosby BM, Rech ME, Yin J, Chen CA, Ali MA, Nguyen HN, Miller JL, Schaaf CP. Journal of Medical Genetics. 2018 Mar 1. pii: jmedgenet-2017-105024.
Christian Schaaf, MD, PhD
Baylor College of Medicine