Tuschl, KarinMeyer, EstherValdivia, Leonardo E.Zhao, NingningDadswell, ChrisAbdul-Sada, AlaaHung, ChristinaSimpson, Michael A.Chong, W. K.Jacques, Thomas S.Woltjer, Randy L.Eaton, SimonGregory, AllisonSanford, LynnKara, EleannaHoulden, HenryCuno, Stephan M.Prokisch, HolgerValletta, LorellaTiranti, ValeriaYounis, RashaMaher, Eamonn R.Spencer, JohnStraatman-Iwanowska, AniaGissen, PaulSelim, Laila A. M.Pintos-Morell, GuillemCoroleu-Lletget, WifredoMohammad, Shekeeb S.Yoganathan, SangeethaDale, Russell C.Thomas, MayaRihel, JasonBodamer, OlafEnns, Caroline A.Hayflick, Susan J.Clayton, Peter T.Mills, Philippa B.Kurian, Manju A.Wilson, Stephen W.2016-07-142016Tuschl, 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/ncomms11601.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:27662059Although 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.en-USJournal Article2016-07-1410.1038/ncomms11601