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Identification of TMEM230 mutations in familial Parkinson's disease.
- Source :
-
Nature genetics [Nat Genet] 2016 Jul; Vol. 48 (7), pp. 733-9. Date of Electronic Publication: 2016 Jun 06. - Publication Year :
- 2016
-
Abstract
- Parkinson's disease is the second most common neurodegenerative disorder without effective treatment. It is generally sporadic with unknown etiology. However, genetic studies of rare familial forms have led to the identification of mutations in several genes, which are linked to typical Parkinson's disease or parkinsonian disorders. The pathogenesis of Parkinson's disease remains largely elusive. Here we report a locus for autosomal dominant, clinically typical and Lewy body-confirmed Parkinson's disease on the short arm of chromosome 20 (20pter-p12) and identify TMEM230 as the disease-causing gene. We show that TMEM230 encodes a transmembrane protein of secretory/recycling vesicles, including synaptic vesicles in neurons. Disease-linked TMEM230 mutants impair synaptic vesicle trafficking. Our data provide genetic evidence that a mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, with implications for understanding the pathogenic mechanism of Parkinson's disease and for developing rational therapies.
- Subjects :
- Age of Onset
Aged
Aged, 80 and over
Amino Acid Sequence
Cells, Cultured
Female
Humans
Male
Middle Aged
Neurons metabolism
Pedigree
Protein Transport genetics
Sequence Homology, Amino Acid
Synaptic Vesicles metabolism
Genetic Predisposition to Disease
Membrane Proteins genetics
Mutation genetics
Neurons pathology
Parkinson Disease genetics
Synaptic Vesicles pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1718
- Volume :
- 48
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 27270108
- Full Text :
- https://doi.org/10.1038/ng.3589