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Oates, E.C.* ; Rossor, A.M.* ; Hafezparast, M.* ; Gonzalez, M.* ; Speziani, F.* ; MacArthur, D.G.* ; Lek, M.* ; Cottenie, E.* ; Scoto, M.* ; Foley, A.R.* ; Hurles, M.* ; Houlden, H.* ; Greensmith, L.* ; Auer-Grumbach, M.* ; Pieber, T.R.* ; Strom, T.M. ; Schule, R.* ; Herrmann, D.N.* ; Sowden, J.E.* ; Acsadi, G.* ; Menezes, M.P.* ; Clarke, N.F.* ; Zuchner, S.* ; Muntoni, F.* ; North, K.N.* ; Reilly, M.M.*

Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia.

Am. J. Hum. Genet. 92, 965-973 (2013)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Dominant congenital spinal muscular atrophy (DCSMA) is a disorder of developing anterior horn cells and shows lower-limb predominance and clinical overlap with hereditary spastic paraplegia (HSP), a lower-limb-predominant disorder of corticospinal motor neurons. We have identified four mutations in bicaudal D homolog 2 (Drosophila) (BICD2) in six kindreds affected by DCSMA, DCSMA with upper motor neuron features, or HSP. BICD2 encodes BICD2, a key adaptor protein that interacts with the dynein-dynactin motor complex, which facilitates trafficking of cellular cargos that are critical to motor neuron development and maintenance. We demonstrate that mutations resulting in amino acid substitutions in two binding regions of BICD2 increase its binding affinity for the cytoplasmic dynein-dynactin complex, which might result in the perturbation of BICD2-dynein-dynactin-mediated trafficking, and impair neurite outgrowth. These findings provide insight into the mechanism underlying both the static and the slowly progressive clinical features and the motor neuron pathology that characterize BICD2-associated diseases, and underscore the importance of the dynein-dynactin transport pathway in the development and survival of both lower and upper motor neurons.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Bicaudal-d ; Transport ; Oogenesis ; Neurons ; Genome ; Form
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Zeitschrift American Journal of Human Genetics, The
Quellenangaben Band: 92, Heft: 6, Seiten: 965-973 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)