TMEM230 variants in Parkinson’s disease (original) (raw)
Nature Genetics
https://doi.org/10.1038/S41588-019-0353-7
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Abstract
AI
The letter critiques a study by Deng et al. which links TMEM230 variants to Parkinson's disease through a familial case. Concerns are raised regarding the presence of unaffected individuals with the TMEM230 variant, potential phenocopies affecting linkage results, and the interpretation of certain mutations that may not be pathogenic. The authors emphasize the need for caution in attributing causal relationships to TMEM230 variants in Parkinson's disease.
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References (5)
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- Vilariño-Güell, C. et al. Hum. Mol. Genet. 23, 1794-1801 (2014).
- Hernandez, D. G., Reed, X. & Singleton, A. B. J. Neurochem. 139, 59-74 (2016).
- Singleton, A. & Hardy, J. Neuron 90, 1154-1163 (2016).
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Identification of TMEM230 mutations in familial Parkinson's disease
Nature genetics, 2016
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 unde...