A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia

In this work, we describe the association of a novel homozygous VPS11 variant with adult‐onset generalized dystonia, providing a detailed clinical report and biological evidence of disease mechanism. Vps11 is a subunit of the homotypic fusion and protein sorting (HOPS) complex, which promotes the fu...

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Detalles Bibliográficos
Autores principales: Monfrini, Edoardo, Cogiamanian, Filippo, Salani, Sabrina, Straniero, Letizia, Fagiolari, Gigliola, Garbellini, Manuela, Carsana, Emma, Borellini, Linda, Biella, Fabio, Moggio, Maurizio, Bresolin, Nereo, Corti, Stefania, Duga, Stefano, Comi, Giacomo P., Aureli, Massimo, Di Fonzo, Alessio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
Materias:
Brief Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048445/
https://www.ncbi.nlm.nih.gov/pubmed/33452836
http://dx.doi.org/10.1002/ana.26021
Descripción
Sumario:In this work, we describe the association of a novel homozygous VPS11 variant with adult‐onset generalized dystonia, providing a detailed clinical report and biological evidence of disease mechanism. Vps11 is a subunit of the homotypic fusion and protein sorting (HOPS) complex, which promotes the fusion of late endosomes and autophagosomes with the lysosome. Functional studies on mutated fibroblasts showed marked lysosomal and autophagic abnormalities, which improved after overexpression of the wild type Vps11 protein. In conclusion, a deleterious VPS11 variant, damaging the autophagic and lysosomal pathways, is the probable genetic cause of a novel form of generalized dystonia. ANN NEUROL 2021;89:834–839

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