Universität zu Köln

Naumann, Marcel, Peikert, Kevin, Guenther, Rene, van der Kooi, Anneke J., Aronica, Eleonora ORCID: 0000-0002-3542-3770, Huebers, Annemarie, Danel, Veronique, Corcia, Philippe, Pan-Montojo, Francisco, Cirak, Sebahattin, Haliloglu, Goeknur, Ludolph, Albert C., Goswami, Anand, Andersen, Peter M., Prudlo, Johannes, Wegner, Florian, Van Damme, Philip, Weishaupt, Jochen H. and Hermann, Andreas . Phenotypes and malignancy risk of different FUS mutations in genetic amyotrophic lateral sclerosis. Ann. Clin. Transl. Neurol.. HOBOKEN: WILEY. ISSN 2328-9503

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Abstract

Objective Mutations in Fused in Sarcoma (FUS or TLS) are the fourth most prevalent in Western European familial amyotrophic lateral sclerosis (ALS) populations and have been associated with causing both early and very late disease onset. FUS aggregation, DNA repair deficiency, and genomic instability are contributors to the pathophysiology of FUS-ALS, but their clinical significance per se and their influence on the clinical variability have yet to be sufficiently investigated. The aim of this study was to analyze genotype-phenotype correlations and malignancy rates in a newly compiled FUS-ALS cohort. Methods We cross-sectionally reviewed FUS-ALS patient histories in a multicenter cohort with 36 novel cases and did a meta-analysis of published FUS-ALS cases reporting the largest genotype-phenotype correlation of FUS-ALS. Results The age of onset (median 39 years, range 11-80) was positively correlated with the disease duration. C-terminal domain mutations were found in 90%. Among all, P525L and truncating/ frameshift mutations most frequently caused juvenile onset, rapid disease progression, and atypical ALS often associated with negative family history while the R521 mutation site was associated with late disease onset and pure spinal phenotype. Malignancies were found in one of 40 patients. Interpretation We report the largest genotype-phenotype correlation of FUS-ALS, which enables a careful prediction of the clinical course in newly diagnosed patients. In this cohort, FUS-ALS patients did not have an increased risk for malignant diseases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Naumann, Marcel UNSPECIFIED UNSPECIFIED UNSPECIFIED Peikert, Kevin UNSPECIFIED UNSPECIFIED UNSPECIFIED Guenther, Rene UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Kooi, Anneke J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Aronica, Eleonora UNSPECIFIED orcid.org/0000-0002-3542-3770 UNSPECIFIED Huebers, Annemarie UNSPECIFIED UNSPECIFIED UNSPECIFIED Danel, Veronique UNSPECIFIED UNSPECIFIED UNSPECIFIED Corcia, Philippe UNSPECIFIED UNSPECIFIED UNSPECIFIED Pan-Montojo, Francisco UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirak, Sebahattin UNSPECIFIED UNSPECIFIED UNSPECIFIED Haliloglu, Goeknur UNSPECIFIED UNSPECIFIED UNSPECIFIED Ludolph, Albert C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Goswami, Anand UNSPECIFIED UNSPECIFIED UNSPECIFIED Andersen, Peter M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Prudlo, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Wegner, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Damme, Philip UNSPECIFIED UNSPECIFIED UNSPECIFIED Weishaupt, Jochen H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hermann, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-128245
DOI:	10.1002/acn3.50930
Journal or Publication Title:	Ann. Clin. Transl. Neurol.
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2328-9503
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ATAXIA-TELANGIECTASIA; DNA-DAMAGE; FUS/TLS; CANCER Multiple languages Clinical Neurology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12824