FUS Mutations in Familial Amyotrophic Lateral Sclerosis in the Netherlands

Ewout J. N. Groen, Michael A. van Es, Paul W. J. van Vught, Wim G. M. Spliet, Jooyeon van Engelen-Lee, Marianne de Visser, John H. J. Wokke, Helenius J. Schelhaas, Roel A. Ophoff, Katsumi Fumoto, R. Jeroen Pasterkamp, Dennis Dooijes, Edwin Cuppen, Jan H. Veldink, Leonard H. van den Berg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Objectives: To assess the frequency of FUS mutations in 52 probands with familial amyotrophic lateral sclerosis (FALS) and to provide careful documentation of clinical characteristics.

Design: FUS mutation analysis was performed using capillary sequencing on all coding regions of the gene in a cohort of patients with FALS. The clinical characteristics of patients carrying FUS mutations were described in detail.

Setting: Three university hospitals in the Netherlands (referral centers for neuromuscular diseases).

Patients: Fifty-two probands from unrelated pedigrees with FALS.

Main Outcome Measure: FUS mutations.

Results: We identified 3 mutations in 4 of 52 probands. We observed 2 previously identified mutations (p.Arg521Cys and p.Arg521His) and 1 novel mutation (p.Ser462Phe). In addition, a p.Gln210His polymorphism was identified in 1 proband and 3 healthy control subjects. Phenotypic analysis demonstrated that patients may lack upper motor neuron signs, which was confirmed at autopsy, and disease survival was short (

Conclusions: We discovered FUS mutations in Dutch patients with FALS and the occurrence of benign variations in the gene. Therefore, caution is warranted when interpreting results in a clinical setting. Although the phenotype associated with FUS mutations is variable, most patients predominantly demonstrate loss of lower motor neurons and have short disease survival.

Original languageEnglish
Pages (from-to)224-230
Number of pages7
JournalArchives of Neurology
Issue number2
Publication statusPublished - Feb 2010

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