Identification of TMEM230 mutations in familial Parkinson's disease

Han Xiang Deng, Yong Shi, Yi Yang, Kreshnik B. Ahmeti, Nimrod Miller, Cao Huang, Lijun Cheng, Hong Zhai, Sheng Deng, Karen Nuytemans, Nicola J. Corbett, Myung Jong Kim, Hao Deng, Beisha Tang, Ziquang Yang, Yanming Xu, Piu Chan, Bo Huang, Xiao Ping Gao, Zhi Song & 14 others Zhenhua Liu, Faisal Fecto, Nailah Siddique, Tatiana Foroud, Joseph Jankovic, Bernardino Ghetti, Daniel A. Nicholson, Dimitri Krainc, Onur Melen, Jeffery M Vance, Margaret A Pericak-Vance, Yong Chao Ma, Ali H. Rajput, Teepu Siddique

Research output: Contribution to journalArticle

85 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)733-739
Number of pages7
JournalNature Genetics
Volume48
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Parkinson Disease
Mutation
Synaptic Vesicles
Chromosomes, Human, Pair 20
Neurons
Secretory Vesicles
Parkinsonian Disorders
Mutant Proteins
Neurodegenerative Diseases
Genes
Proteins

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics

Cite this

Deng, H. X., Shi, Y., Yang, Y., Ahmeti, K. B., Miller, N., Huang, C., ... Siddique, T. (2016). Identification of TMEM230 mutations in familial Parkinson's disease. Nature Genetics, 48(7), 733-739. https://doi.org/10.1038/ng.3589

Identification of TMEM230 mutations in familial Parkinson's disease. / Deng, Han Xiang; Shi, Yong; Yang, Yi; Ahmeti, Kreshnik B.; Miller, Nimrod; Huang, Cao; Cheng, Lijun; Zhai, Hong; Deng, Sheng; Nuytemans, Karen; Corbett, Nicola J.; Kim, Myung Jong; Deng, Hao; Tang, Beisha; Yang, Ziquang; Xu, Yanming; Chan, Piu; Huang, Bo; Gao, Xiao Ping; Song, Zhi; Liu, Zhenhua; Fecto, Faisal; Siddique, Nailah; Foroud, Tatiana; Jankovic, Joseph; Ghetti, Bernardino; Nicholson, Daniel A.; Krainc, Dimitri; Melen, Onur; Vance, Jeffery M; Pericak-Vance, Margaret A; Ma, Yong Chao; Rajput, Ali H.; Siddique, Teepu.

In: Nature Genetics, Vol. 48, No. 7, 01.07.2016, p. 733-739.

Research output: Contribution to journalArticle

Deng, HX, Shi, Y, Yang, Y, Ahmeti, KB, Miller, N, Huang, C, Cheng, L, Zhai, H, Deng, S, Nuytemans, K, Corbett, NJ, Kim, MJ, Deng, H, Tang, B, Yang, Z, Xu, Y, Chan, P, Huang, B, Gao, XP, Song, Z, Liu, Z, Fecto, F, Siddique, N, Foroud, T, Jankovic, J, Ghetti, B, Nicholson, DA, Krainc, D, Melen, O, Vance, JM, Pericak-Vance, MA, Ma, YC, Rajput, AH & Siddique, T 2016, 'Identification of TMEM230 mutations in familial Parkinson's disease', Nature Genetics, vol. 48, no. 7, pp. 733-739. https://doi.org/10.1038/ng.3589
Deng HX, Shi Y, Yang Y, Ahmeti KB, Miller N, Huang C et al. Identification of TMEM230 mutations in familial Parkinson's disease. Nature Genetics. 2016 Jul 1;48(7):733-739. https://doi.org/10.1038/ng.3589
Deng, Han Xiang ; Shi, Yong ; Yang, Yi ; Ahmeti, Kreshnik B. ; Miller, Nimrod ; Huang, Cao ; Cheng, Lijun ; Zhai, Hong ; Deng, Sheng ; Nuytemans, Karen ; Corbett, Nicola J. ; Kim, Myung Jong ; Deng, Hao ; Tang, Beisha ; Yang, Ziquang ; Xu, Yanming ; Chan, Piu ; Huang, Bo ; Gao, Xiao Ping ; Song, Zhi ; Liu, Zhenhua ; Fecto, Faisal ; Siddique, Nailah ; Foroud, Tatiana ; Jankovic, Joseph ; Ghetti, Bernardino ; Nicholson, Daniel A. ; Krainc, Dimitri ; Melen, Onur ; Vance, Jeffery M ; Pericak-Vance, Margaret A ; Ma, Yong Chao ; Rajput, Ali H. ; Siddique, Teepu. / Identification of TMEM230 mutations in familial Parkinson's disease. In: Nature Genetics. 2016 ; Vol. 48, No. 7. pp. 733-739.
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