dc.contributor.author | Tuerk, Matthias | |
dc.contributor.author | Schroeder, Rolf | |
dc.contributor.author | Khuller, Katharina | |
dc.contributor.author | Hofmann, Andreas | |
dc.contributor.author | Berwanger, Carolin | |
dc.contributor.author | Ludolph, Albert C | |
dc.contributor.author | Dekomien, Gabriele | |
dc.contributor.author | Mueller, Kathrin | |
dc.contributor.author | Weishaupt, Jochen H | |
dc.contributor.author | Thiel, Christian T | |
dc.contributor.author | Clemen, Christoph S | |
dc.date.accessioned | 2017-09-14T00:38:05Z | |
dc.date.available | 2017-09-14T00:38:05Z | |
dc.date.issued | 2017 | |
dc.identifier.issn | 0197-4580 | |
dc.identifier.doi | 10.1016/j.neurobiolaging.2017.04.023 | |
dc.identifier.uri | http://hdl.handle.net/10072/346255 | |
dc.description.abstract | Mutations 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.relation.ispartofpagefrom | 213.e1 | |
dc.relation.ispartofpageto | 213.e5 | |
dc.relation.ispartofjournal | Neurobiology of Aging | |
dc.relation.ispartofvolume | 56 | |
dc.subject.fieldofresearch | Clinical sciences | |
dc.subject.fieldofresearch | Clinical sciences not elsewhere classified | |
dc.subject.fieldofresearch | Neurosciences | |
dc.subject.fieldofresearchcode | 3202 | |
dc.subject.fieldofresearchcode | 320299 | |
dc.subject.fieldofresearchcode | 3209 | |
dc.title | Genetic analysis of VCP and WASH complex genes in a German cohort of sporadic ALS-FTD patients | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
dcterms.license | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.description.version | Accepted 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.hasfulltext | Full Text | |
gro.griffith.author | Hofmann, Andreas | |