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dc.contributor.authorTuerk, Matthias
dc.contributor.authorSchroeder, Rolf
dc.contributor.authorKhuller, Katharina
dc.contributor.authorHofmann, Andreas
dc.contributor.authorBerwanger, Carolin
dc.contributor.authorLudolph, Albert C
dc.contributor.authorDekomien, Gabriele
dc.contributor.authorMueller, Kathrin
dc.contributor.authorWeishaupt, Jochen H
dc.contributor.authorThiel, Christian T
dc.contributor.authorClemen, Christoph S
dc.date.accessioned2017-09-14T00:38:05Z
dc.date.available2017-09-14T00:38:05Z
dc.date.issued2017
dc.identifier.issn0197-4580
dc.identifier.doi10.1016/j.neurobiolaging.2017.04.023
dc.identifier.urihttp://hdl.handle.net/10072/346255
dc.description.abstractMutations of the human valosin-containing protein, p97 (VCP) and Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex genes cause motor neuron and cognitive impairment disorders. Here, we analyzed a cohort of German patients with sporadic amyotrophic lateral sclerosis and frontotemporal lobar degeneration comorbidity (ALS/FTD) for VCP and WASH complex gene mutations. Next-generation panel sequencing of VCP, WASH1, FAM21C, CCDC53, SWIP, strumpellin, F-actin capping protein of muscle Z-line alfa 1 (CAPZA1), and CAPZB genes was performed in 43 sporadic ALS/FTD patients. Subsequent analyses included Sanger sequencing, in silico analyses, real-time PCR, and CCDC53 immunoblotting. We identified 1 patient with the heterozygous variant c.26C>T in CAPZA1, predicted to result in p.Ser9Leu, and a second with the heterozygous start codon variant c.2T>C in CCDC53. In silico analysis predicted structural changes in the N-terminus of CAPZα1, which may interfere with CAPZα:CAPZβ dimerization. Though the translation initiation codon of CCDC53 is mutated, real-time PCR and immunoblotting did neither reveal any evidence for a CCDC53 haploinsufficiency nor for aberrant CCDC53 protein species. Moreover, a disease-causing C9orf72 repeat expansion mutation was later on identified in this patient. Thus, with the exception of a putatively pathogenic heterozygous c.26C>T CAPZA1 variant, our genetic analysis did not reveal mutations in VCP and the remaining WASH complex subunits.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom213.e1
dc.relation.ispartofpageto213.e5
dc.relation.ispartofjournalNeurobiology of Aging
dc.relation.ispartofvolume56
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchClinical sciences not elsewhere classified
dc.subject.fieldofresearchNeurosciences
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode320299
dc.subject.fieldofresearchcode3209
dc.titleGenetic analysis of VCP and WASH complex genes in a German cohort of sporadic ALS-FTD patients
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.description.versionAccepted Manuscript (AM)
gro.rights.copyright© 2017 Federation of European Biochemical Societies, published by Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorHofmann, Andreas


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