Universität zu Köln

Huebers, Annemarie, Just, Walter, Rosenbohm, Angela, Mueller, Kathrin, Marroquin, Nicolai, Goebel, Ingrid, Hoegel, Josef, Thiele, Holger, Altmueller, Janine, Nuernberg, Peter, Weishaupt, Jochen H., Kubisch, Christian ORCID: 0000-0003-4220-0978, Ludolph, Albert C. and Volk, Alexander E. (2015). De novo FUS mutations are the most frequent genetic cause in early-onset German ALS patients. Neurobiol. Aging, 36 (11). NEW YORK: ELSEVIER SCIENCE INC. ISSN 1558-1497

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Abstract

In amyotrophic lateral sclerosis (ALS) patients with known genetic cause, mutations in chromosome 9 open reading frame 72 (C9orf72) and superoxide dismutase 1 (SOD1) account for most familial and late-onset sporadic cases, whereas mutations in fused in sarcoma (FUS) can be identified in just around 5% of familial and 1% of overall sporadic cases. There are only few reports on de novo FUS mutations in juvenile ALS patients. To date, no systematic evaluation on the frequency of de novo FUS mutations in early-onset ALS patients has been conducted. Here, we screened a cohort of 14 early-onset sporadic ALS patients (onset age <35 years) to determine the frequency of mutations in C9orf72, SOD1, and FUS in this defined patient cohort. All patients were recruited prospectively by a single center in a period of 38 months. No mutations were detected in SOD1 or C9orf72; however, we identified 6 individuals (43%) carrying a heterozygous FUS mutation including 1 mutation that has not been described earlier (c.1504delG [p.Asp502Thrfs*27]). Genetic testing of parents was possible in 5 families and revealed that the mutations in these patients arose de novo. Three of the 6 identified patients presented with initial bulbar symptoms. Our study identifies FUS mutations as the most frequent genetic cause in early-onset ALS. Genetic testing of FUS thus seems indicated in sporadic early-onset ALS patients especially if showing predominant bulbar symptoms and an aggressive disease course. (C) 2015 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Huebers, Annemarie UNSPECIFIED UNSPECIFIED UNSPECIFIED Just, Walter UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenbohm, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Marroquin, Nicolai UNSPECIFIED UNSPECIFIED UNSPECIFIED Goebel, Ingrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoegel, Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Weishaupt, Jochen H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubisch, Christian UNSPECIFIED orcid.org/0000-0003-4220-0978 UNSPECIFIED Ludolph, Albert C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Volk, Alexander E. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-388949
DOI:	10.1016/j.neurobiolaging.2015.08.005
Journal or Publication Title:	Neurobiol. Aging
Volume:	36
Number:	11
Date:	2015
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 AMYOTROPHIC-LATERAL-SCLEROSIS; HEXANUCLEOTIDE REPEAT; TRUNCATING MUTATIONS; FUS/TLS; C9ORF72; PHENOTYPE; MISSENSE; TARDBP; SOD-1; ANG Multiple languages Geriatrics & Gerontology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38894