Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Tuerk, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Khuller, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Andreas UNSPECIFIED orcid.org/0000-0003-4408-5467 UNSPECIFIED Berwanger, Carolin UNSPECIFIED UNSPECIFIED UNSPECIFIED Ludolph, Albert C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dekomien, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Weishaupt, Jochen H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiel, Christian T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Clemen, Christoph S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language MUTATION; SEQUENCE; DISEASE; IDENTIFICATION; ASSOCIATION; PREDICTION; REGULATORS; VPS35 Multiple languages Geriatrics & Gerontology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22426