Journal article
Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2
Alexander M Rossor, Emily C Oates, Hannah K Salter, Yang Liu, Sinead M Murphy, Rebecca Schule, Michael A Gonzalez, Mariacristina Scoto, Rahul Phadke, Caroline A Sewry, Henry Houlden, Albena Jordanova, Iyailo Tournev, Teodora Chamova, Ivan Litvinenko, Stephan Zuchner, David N Herrmann, Julian Blake, Janet E Sowden, Gyuda Acsadi Show all
BRAIN | OXFORD UNIV PRESS | Published : 2015
DOI: 10.1093/brain/awu356
Abstract
Spinal muscular atrophy is a disorder of lower motor neurons, most commonly caused by recessive mutations in SMN1 on chromosome 5q. Cases without SMN1 mutations are subclassified according to phenotype. Spinal muscular atrophy, lower extremity-predominant, is characterized by lower limb muscle weakness and wasting, associated with reduced numbers of lumbar motor neurons and is caused by mutations in DYNC1H1, which encodes a microtubule motor protein in the dynein-dynactin complex and one of its cargo adaptors, BICD2. We have now identified 32 patients with BICD2 mutations from nine different families, providing detailed insights into the clinical phenotype and natural history of BICD2 diseas..
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Awarded by office of Rare Diseases
Awarded by European Union within the 7th European Community Framework program
Awarded by E-Rare-Network NEUROLIPID
Awarded by Centre for Clinical Research (IZKF) Tubingen
Awarded by National Institutes of Neurological Diseases and Stroke for CReATe RDCRC
Awarded by FWF
Awarded by MRC Centre grant
Awarded by University of Antwerp (TOP BOF)
Awarded by Fund for Scientific Research-Flanders (FWO)
Awarded by NHMRC Centre for Research Excellence grant
Awarded by NHMRC
Awarded by Inherited neuropathies Consortium RDCRN
Awarded by National Human Genome Research Institute of the National Institutes of Health (NIH) (Medical Sequencing Program)
Awarded by MRC
Awarded by Austrian Science Fund (FWF)
Awarded by Medical Research Council
Awarded by Muscular Dystrophy UK
Awarded by Rosetrees Trust
Funding Acknowledgements
A.M.R. is grateful for his fellowship funding from the National Institutes of Neurological Diseases and Stroke and office of Rare Diseases (U54NS065712). He has also been in receipt of an IPSEN clinical research fellowship. E.C.O. is gratefully funded by a National Health and Medical Research (NHMRC) postgraduate scholarship. R.S. is supported by the European Union within the 7th European Community Framework program through funding for a Marie Curie International Outgoing Fellowship (grant PIOF-GA-2012-326681) and the E-Rare-Network NEUROLIPID 01GM1408B. Centre for Clinical Research (IZKF) Tubingen (grant 1970-0-0) and by the National Institutes of Neurological Diseases and Stroke for CReATe RDCRC (U54-NS-092091). M.A.G. is supported by an FWF (P23223-B19) grant for her research. M.P.M. is supported by a grant from the Thyne Reid Foundation. M.M.R. is grateful to the Medical Research Council (MRC), MRC Centre grant (G0601943), and the National Institutes of Neurological Diseases and Stroke and office of Rare Diseases (U54NS065712) for their support. S.M.M. received fellowship funding from the National Institutes of Neurological Diseases and Stroke and office of Rare Diseases (U54NS065712). Some of this work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. A.J. is funded in part by the University of Antwerp (TOP BOF grant 29069), the Fund for Scientific Research-Flanders (FWO grant G054313N) and the Association Belge contre les Maladies Neuromusculaires (ABMM). N.F.C. and K.N.N. are supported by NHMRC Centre for Research Excellence grant #1031983 and NHMRC Project Grant #1022707. F.M. is supported by the Great Ormond Street Hospital Children's Charity, and the associated Biomedical Research centre. Genetic testing of families 2, 4, 6, 7, and 8 by A/Prof Stephan Zuchner's team was supported by the Inherited neuropathies Consortium RDCRN, NINDS-1U54NS0657. Exome sequencing of AUS1 kindred members was supported by a grant from the National Human Genome Research Institute of the National Institutes of Health (NIH) (Medical Sequencing Program grant U54 HG003067 to the Broad Institute PI, Lander). S.L.B., H.K.S. and Y.L. were supported by the MRC (U105178790) and a Lister Institute research prize.