Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia

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Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia

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Title: Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia
Author: Tuschl, Karin; Meyer, Esther; Valdivia, Leonardo E.; Zhao, Ningning; Dadswell, Chris; Abdul-Sada, Alaa; Hung, Christina Y.; Simpson, Michael A.; Chong, W. K.; Jacques, Thomas S.; Woltjer, Randy L.; Eaton, Simon; Gregory, Allison; Sanford, Lynn; Kara, Eleanna; Houlden, Henry; Cuno, Stephan M.; Prokisch, Holger; Valletta, Lorella; Tiranti, Valeria; Younis, Rasha; Maher, Eamonn R.; Spencer, John; Straatman-Iwanowska, Ania; Gissen, Paul; Selim, Laila A. M.; Pintos-Morell, Guillem; Coroleu-Lletget, Wifredo; Mohammad, Shekeeb S.; Yoganathan, Sangeetha; Dale, Russell C.; Thomas, Maya; Rihel, Jason; Bodamer, Olaf A.; Enns, Caroline A.; Hayflick, Susan J.; Clayton, Peter T.; Mills, Philippa B.; Kurian, Manju A.; Wilson, Stephen W.

Note: Order does not necessarily reflect citation order of authors.

Citation: Tuschl, K., E. Meyer, L. E. Valdivia, N. Zhao, C. Dadswell, A. Abdul-Sada, C. Y. Hung, et al. 2016. “Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia.” Nature Communications 7 (1): 11601. doi:10.1038/ncomms11601. http://dx.doi.org/10.1038/ncomms11601.
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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.
Published Version: doi:10.1038/ncomms11601
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894980/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:27662059
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