Title |
Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia
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Published in |
Nature Communications, May 2016
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DOI | 10.1038/ncomms11601 |
Pubmed ID | |
Authors |
Karin Tuschl, Esther Meyer, Leonardo E. Valdivia, Ningning Zhao, Chris Dadswell, Alaa Abdul-Sada, Christina Y. Hung, Michael A. Simpson, W. K. Chong, Thomas S. Jacques, Randy L. Woltjer, Simon Eaton, Allison Gregory, Lynn Sanford, Eleanna Kara, Henry Houlden, Stephan M. Cuno, Holger Prokisch, Lorella Valletta, Valeria Tiranti, Rasha Younis, Eamonn R. Maher, John Spencer, Ania Straatman-Iwanowska, Paul Gissen, Laila A. M. Selim, Guillem Pintos-Morell, Wifredo Coroleu-Lletget, Shekeeb S. Mohammad, Sangeetha Yoganathan, Russell C. Dale, Maya Thomas, Jason Rihel, Olaf A. Bodamer, Caroline A. Enns, Susan J. Hayflick, Peter T. Clayton, Philippa B. Mills, Manju A. Kurian, Stephen W. Wilson |
Abstract |
Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates. |
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Geographical breakdown
Country | Count | As % |
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United Kingdom | 3 | 21% |
Spain | 2 | 14% |
Netherlands | 1 | 7% |
Malaysia | 1 | 7% |
China | 1 | 7% |
United States | 1 | 7% |
Unknown | 5 | 36% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 8 | 57% |
Scientists | 5 | 36% |
Science communicators (journalists, bloggers, editors) | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Mexico | 1 | <1% |
Unknown | 231 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 35 | 15% |
Researcher | 31 | 13% |
Student > Bachelor | 30 | 13% |
Student > Master | 29 | 13% |
Student > Doctoral Student | 12 | 5% |
Other | 40 | 17% |
Unknown | 55 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 41 | 18% |
Agricultural and Biological Sciences | 32 | 14% |
Neuroscience | 27 | 12% |
Medicine and Dentistry | 25 | 11% |
Chemistry | 10 | 4% |
Other | 31 | 13% |
Unknown | 66 | 28% |