A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia.
Adult
Age of Onset
Amino Acid Sequence
Autophagy
/ genetics
Brain
/ diagnostic imaging
DNA
/ genetics
Dystonia
/ diagnostic imaging
Endosomes
/ pathology
Fibroblasts
/ pathology
Genetic Variation
Homozygote
Humans
Lysosomes
/ pathology
Magnetic Resonance Imaging
Mutation
Pedigree
Phagosomes
/ pathology
Vesicular Transport Proteins
/ genetics
Exome Sequencing
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
11
01
2021
received:
01
10
2020
accepted:
13
01
2021
pubmed:
17
1
2021
medline:
26
5
2021
entrez:
16
1
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33452836
doi: 10.1002/ana.26021
pmc: PMC8048445
doi:
Substances chimiques
VPS11 protein, human
0
Vesicular Transport Proteins
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
834-839Informations de copyright
© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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