1. Identification of TMEM230 mutations in familial Parkinson's disease
- Author
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Jeffery M. Vance, Lijun Cheng, Hong Zhai, Cao Huang, Sheng Deng, Bo Huang, Kreshnik B. Ahmeti, Zhi Song, Joseph Jankovic, Onur Melen, Teepu Siddique, Nailah Siddique, Myung Jong Kim, Daniel A. Nicholson, Zhenhua Liu, Xiao Ping Gao, Nicola J. Corbett, Dimitri Krainc, Han Xiang Deng, Karen Nuytemans, Yanming Xu, Beisha Tang, Bernardino Ghetti, Margaret A. Pericak-Vance, Piu Chan, Yong Chao Ma, Yong Shi, Tatiana Foroud, Nimrod Miller, Ali H. Rajput, Ziquang Yang, Yi Yang, Hao Deng, and Faisal Fecto
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Parkinson's disease ,Dopamine ,Locus (genetics) ,Disease ,Biology ,Synaptic vesicle ,Article ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Amino Acid Sequence ,Age of Onset ,Letter to the Editor ,Cells, Cultured ,Aged ,Aged, 80 and over ,Neurons ,Sequence Homology, Amino Acid ,Membrane Proteins ,Parkinson Disease ,Middle Aged ,medicine.disease ,Transmembrane protein ,3. Good health ,Transport protein ,Pedigree ,Protein Transport ,030104 developmental biology ,Mutation ,Medical genetics ,Female ,Synaptic Vesicles ,030217 neurology & neurosurgery - 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 remain largely elusive. Here, we report a novel genetic locus for an autosomal dominant, clinically typical and Lewy body confirmed Parkinson’s disease on the short arm of chromosome 20 (20pter-p12) and TMEM230 as the disease-causing gene. We show that TMEM230 encodes a transmembrane protein of secretory/recycling vesicles, including synaptic vesicles in neurons. The disease-linked TMEM230 mutants impair synaptic vesicle trafficking. Our data provide the first genetic evidence that a mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson’s disease, with novel implications in understanding the pathogenic mechanism of Parkinson’s disease and for developing rational therapies.
- Published
- 2016