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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)
Verlagsversion Forschungsdaten 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Nature Communications
Quellenangaben Band: 7, Heft: , Seiten: , Artikelnummer: 11601 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)