Tuerk, Matthias, Schroeder, Rolf, Khuller, Katharina, Hofmann, Andreas ORCID: 0000-0003-4408-5467, Berwanger, Carolin, Ludolph, Albert C., Dekomien, Gabriele, Mueller, Kathrin, Weishaupt, Jochen H., Thiel, Christian T. and Clemen, Christoph S. (2017). Genetic analysis of VCP and WASH complex genes in a German cohort of sporadic ALS-FTD patients. Neurobiol. Aging, 56. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1558-1497

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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 CAPZa1, which may interfere with CAPZa: CAPZb 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. (C) 2017 Elsevier Inc. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tuerk, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeder, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khuller, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann, AndreasUNSPECIFIEDorcid.org/0000-0003-4408-5467UNSPECIFIED
Berwanger, CarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ludolph, Albert C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dekomien, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weishaupt, Jochen H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiel, Christian T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clemen, Christoph S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-224266
DOI: 10.1016/j.neurobiolaging.2017.04.023
Journal or Publication Title: Neurobiol. Aging
Volume: 56
Date: 2017
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1558-1497
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MUTATION; SEQUENCE; DISEASE; IDENTIFICATION; ASSOCIATION; PREDICTION; REGULATORS; VPS35Multiple languages
Geriatrics & Gerontology; NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22426

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