Gene/phenotype/disorder under study
MAGEL2 / All phenotypes / OMIM : 615547 / ORPHA:398069
Abstract
Schaaf-Yang syndrome (SHFYNG) is caused by heterozygous mutation in the MAGEL2 gene. The transmission pattern of SHFYNG is consistent with autosomal dominant inheritance with maternal imprinting, being the gene expressed only by the paternal allele.
The neurodevelopmental disorders Prader-Willi syndrome (PWS) and SHFYNG both arise from genomic alterations within human chromosome 15q11-q13. A deletion of the SNORD116 cluster, encoding small nucleolar RNAs, or frameshift mutations within MAGEL2 result in closely related phenotypes in individuals with PWS or SYS, respectively.
Recently, a patient with an isolated deletion of MAGEL2, NDN, and MKRN3 who exhibits the full PWS phenotype, including neonatal hypotonia, developmental delay, hyperphagia, obesity, and behavioral issues, was reported.
Today, about 200 patients are reported, with few detailed descriptions. The progression into adulthood is poorly understood, leaving a significant gap in terms of prognosis. Furthermore, as differential methylation of this is gene is responsible from sex differences in high functioning autistic patients, we want to explore more the phenotype- genotype relationship.
If you have patients with a MAGEL2 variant (ACMG class 4 or 5 pathogenic or likely pathogenic) possibly with characterisation of parent origin and would like to participate in this study, please contact us.
Coordinating clinicians
Alessandra Renieri – alessandra.renieri@unisi.it
Stefano Stagi – stefano.stagi@unifi.it
Institution
Azienda Ospedaliera Universitaria Senese AOUSeneseAzienda Ospedaliera Universitaria Meyer AOUMeyer
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: No
2- Resampling of patients: No
3- Linked to a translational/basic research project: No