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cc-by-nc (c)  Centeno-Pla Monica et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/217097

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

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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.

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CENTENO-PLA, Mónica, ALCAIDE-CONSUEGRA, Estefanía, GIBSON, Sophie, PRAT-PLANAS, Aina, GUTIÉRREZ-ÁVILA, Juan diego, GRINBERG VAISMAN, Daniel raúl, URREIZTI, Roser, RABIONET JANSSEN, Raquel, BALCELLS COMAS, Susana. Subcellular localisation of truncated MAGEL2 proteins: insight into the molecular pathology of Schaaf-Yang syndrome. _Journal of Medical Genetics_. 2024. Vol. 61, núm. 8, pàgs. 780-782. [consulta: 10 de desembre de 2025]. ISSN: 0022-2593. [Disponible a: https://hdl.handle.net/2445/217097]

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