Patients with MAGEL2 variants shared several features with PWS, such as neonatal hypotonia, poor suck, and obesity; however, there were also unique features, including arthrogryposis and a failure to acquire meaningful words.
Pathogenic variants in the paternal copy of MAGEL2 cause Schaaf-Yang syndrome (SHFYNG), a neurodevelopmental disorder related to Prader-Willi syndrome (PWS).
Genetic underpinning of PWS involves deletion of a chromosomal region with several genes, including MAGEL2, which is abundantly expressed in the hypothalamus.
Truncating variants of the MAGEL2 gene, one of the protein-coding genes within the Prader-Willi syndrome (PWS) critical region on chromosome 15q11, cause Schaaf-Yang syndrome (SYS)-a neurodevelopmental disorder that shares several clinical features with PWS.
In the present study, we investigated whether OEA contributes to feeding dysregulation in Magel2<sup>m+/p-</sup> (Magel2 KO) mice, an animal model of PWS.
This review provides an overview of the MAGE protein family of ubiquitin ligases regulators and details the molecular and cellular role of MAGEL2 in ubiquitination, actin regulation and endosomal sorting processes, as well as MAGEL2 implications in PWS and SHFYNG disorders.
Here, we show that paternal MAGEL2 mutations are also responsible for lethal AMC, recapitulating the clinical spectrum of PWS and suggesting that MAGEL2 is a PWS-determining gene.
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.
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.
Our results suggest that loss of MAGEL2 contributes to the reproductive deficits seen in people with PWS, and further highlights the role of normal circadian rhythm in the maintenance of fertility.
Four protein-encoding genes (MKRN3, MAGEL2, NDN and SNURF-SNRPN) and several small nucleolar (sno) RNA genes (HBII-13, HBII-436, HBII-85, HBII-438A, HBII-438B and HBII-52) are expressed from the paternal chromosome only but their contribution to PWS is unclear.
We further suggest that loss of necdin contributes to the neurological phenotype of PWS, and raise the possibility that co-deletion of necdin and the related protein Magel2 may explain the lack of single gene mutations in PWS.