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 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.

A novel homozygous VPS11 variant may cause generalized dystonia / E. Monfrini, F. Cogiamanian, S. Salani, L. Straniero, G. Fagiolari, M. Garbellini, E. Carsana, L. Borellini, F. Biella, M. Moggio, N. Bresolin, S. Corti, S. Duga, G.P. Comi, M. Aureli, A. Di Fonzo. - In: ANNALS OF NEUROLOGY. - ISSN 0364-5134. - (2021). [Epub ahead of print] [10.1002/ana.26021]

A novel homozygous VPS11 variant may cause generalized dystonia

E. Monfrini;F. Cogiamanian;S. Salani;L. Straniero;E. Carsana;L. Borellini;F. Biella;N. Bresolin;S. Corti;S. Duga;G.P. Comi;M. Aureli;
2021

Abstract

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 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.
Settore MED/26 - Neurologia
16-gen-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/809941
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