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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.

SUBMITTER: Monfrini E

PROVIDER: S-EPMC8048445 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia.

Monfrini Edoardo E Cogiamanian Filippo F Salani Sabrina S Straniero Letizia L Fagiolari Gigliola G Garbellini Manuela M Carsana Emma E Borellini Linda L Biella Fabio F Moggio Maurizio M Bresolin Nereo N Corti Stefania S Duga Stefano S Comi Giacomo P GP Aureli Massimo M Di Fonzo Alessio A

Annals of neurology 20210202 4

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 ...[more]

PMID: 33452836

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