De novo FUS mutations are the most frequent genetic cause in early-onset German ALS patients

Item Type:	Article
Title:	De novo FUS mutations are the most frequent genetic cause in early-onset German ALS patients
Creators Name:	Hübers, A. and Just, W. and Rosenbohm, A. and Müller, K. and Marroquin, N. and Goebel, I. and Högel, J. and Thiele, H. and Altmüller, J. and Nürnberg, P. and Weishaupt, J.H. and Kubisch, C. and Ludolph, A.C. and Volk, A.E.
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.
Keywords:	Amyotrophic Lateral Sclerosis (ALS), Early Onset, Fused In Sarcoma (FUS), De Novo Mutation, Genetic Testing
Source:	Neurobiology of Aging
ISSN:	0197-4580
Publisher:	Elsevier
Volume:	36
Number:	11
Page Range:	3117.e1-3117.e6
Date:	November 2015
Official Publication:	https://doi.org/10.1016/j.neurobiolaging.2015.08.005
PubMed:	View item in PubMed

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