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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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
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author 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
author_facet 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
author_sort Monfrini, Edoardo
collection PubMed
description 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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spelling pubmed-80484452021-04-16 A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia 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 Ann Neurol Brief Communications 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 John Wiley & Sons, Inc. 2021-02-02 2021-04 /pmc/articles/PMC8048445/ /pubmed/33452836 http://dx.doi.org/10.1002/ana.26021 Text en © 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Brief Communications
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
A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia
title A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia
title_full A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia
title_fullStr A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia
title_full_unstemmed A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia
title_short A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia
title_sort novel homozygous vps11 variant may cause generalized dystonia
topic Brief Communications
url 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
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