2. Academic Validation
  3. A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia

A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia

  • Ann Neurol. 2021 Apr;89(4):834-839. doi: 10.1002/ana.26021.
Edoardo Monfrini 1 2,  Filippo Cogiamanian 3,  Sabrina Salani 1 2,  Letizia Straniero 4,  Gigliola Fagiolari 5 6,  Manuela Garbellini 2 6,  Emma Carsana 7,  Linda Borellini 3,  Fabio Biella 1 2,  Maurizio Moggio 5,  Nereo Bresolin 1 2,  Stefania Corti 1 2,  Stefano Duga 4 8,  Giacomo P Comi 1 5,  Massimo Aureli 7,  Alessio Di Fonzo 1 2
Affiliations

Affiliations

  • 1 Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy.
  • 2 Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
  • 3 Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Neuropathophysiology, University of Milan, Milan, Italy.
  • 4 Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • 5 Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Diseases Unit, Milan, Italy.
  • 6 Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Healthcare Professionals Department, Milan, Italy.
  • 7 Dip. Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, LITA, Via Fratelli Cervi 93, Segrate, Milan, Italy.
  • 8 Humanitas Clinical and Research Center, IRCCS, Milan, Italy.
PMID: 33452836 DOI: 10.1002/ana.26021
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 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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