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Tuschl, K.* ; Meyer, E.* ; Valdivia, L.E.* ; Zhao, N.* ; Dadswell, C.* ; Abdul-Sada, A.* ; Hung, C.Y.* ; Simpson, M.A.* ; Chong, W.K.* ; Jacques, T.S.* ; Woltjer, R.L.* ; Eaton, S.* ; Gregory, A.* ; Sanford, L.* ; Kara, E.* ; Houlden, H.* ; Cuno, S.M. ; Prokisch, H. ; Valletta, L.* ; Tiranti, V.* ; Younis, R.* ; Maher, E.R.* ; Spencer, J.* ; Straatman-Iwanowska, A.* ; Gissen, P.* ; Selim, L.A.M.* ; Pintos-Morell, G.* ; Coroleu-Lletget, W.* ; Mohammad, S.S.* ; Yoganathan, S.* ; Dale, R.C.* ; Thomas, M.* ; Rihel, J.* ; Bodamer, O.A.* ; Enns, C.A.* ; Hayflick, S.J.* ; Clayton, P.T.* ; Mills, P.B.* ; Kurian, M.A.* ; Wilson, S.W.*

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

Nat. Commun. 7:11601 (2016)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Blood-brain-barrier; Alpha-synuclein; Zinc Transporters; Hepatic Cirrhosis; Gene-expression; Liv-1 Subfamily; Whole-blood; Icp-ms; Zebrafish; Zip14
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 7, Issue: , Pages: , Article Number: 11601 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)