Login / Signup

Subcellular localisation of truncated MAGEL2 proteins: insight into the molecular pathology of Schaaf-Yang syndrome.

Mónica Centeno-PlaEstefanía Alcaide-ConsuegraSophie GibsonAina Prat-PlanasJuan Diego Gutiérrez-ÁvilaDaniel GrinbergRoser UrreiztiRaquel Rabionet JanssenSusanna Balcells
Published in: Journal of medical genetics (2024)
Schaaf-Yang syndrome (SYS) is an ultra-rare neurodevelopmental disorder caused by truncating mutations in MAGEL2 Heterologous expression of wild-type (WT) or a truncated (p.Gln638*) C-terminal HA-tagged MAGEL2 revealed a shift from a primarily cytoplasmic to a more nuclear localisation for the truncated protein variant. We now extend this analysis to six additional SYS mutations on a N-terminal FLAG-tagged MAGEL2. Our results replicate and extend our previous findings, showing that all the truncated MAGEL2 proteins consistently display a predominant nuclear localisation, irrespective of the C-terminal or N-terminal position and the chemistry of the tag. The variants associated with arthrogryposis multiplex congenita display a more pronounced nuclear retention phenotype, suggesting a correlation between clinical severity and the degree of nuclear mislocalisation. These results point to a neomorphic effect of truncated MAGEL2, which might contribute to the pathogenesis of SYS.
Keyphrases
  • wild type
  • poor prognosis
  • case report
  • high resolution
  • high throughput
  • copy number
  • gene expression
  • dna methylation
  • amino acid
  • protein protein
  • single molecule
  • real time pcr
  • saccharomyces cerevisiae