A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia.

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.

• Authors: Edoardo Monfrini, Filippo Cogiamanian, Sabrina Salani, Letizia Straniero, Gigliola Fagiolari, Manuela Garbellini, Emma Carsana, Linda Borellini, Fabio Biella, Maurizio Moggio, Nereo Bresolin, Stefania Corti, Stefano Duga, Giacomo P Comi, Massimo Aureli, Alessio Di Fonzo
• Journal: Annals of neurology (Ann Neurol) Vol. 89 Issue 4 Pg. 834-839 (Apr 2021) ISSN: 1531-8249 [Electronic] United States
• PMID: 33452836 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Chemical References

• VPS11 protein, human
• Vesicular Transport Proteins
• DNA

Topics

• Adult
• Age of Onset
• Amino Acid Sequence
• Autophagy (genetics)
• Brain (diagnostic imaging)
• DNA (genetics)
• Dystonia (diagnostic imaging, etiology, genetics)
• Endosomes (pathology)
• Fibroblasts (pathology)
• Genetic Variation
• Homozygote
• Humans
• Lysosomes (pathology)
• Magnetic Resonance Imaging
• Mutation
• Pedigree
• Phagosomes (pathology)
• Vesicular Transport Proteins (genetics)
• Exome Sequencing