FUS Mutations in Familial Amyotrophic Lateral Sclerosis in the Netherlands.
Groen, Ewout J. MSc; van Es, Michael A. MD; van Vught, Paul W. PhD; Spliet, Wim G. MD; van Engelen-Lee, Jooyeon MD; de Visser, Marianne MD, PhD; Wokke, John H. MD, PhD; Schelhaas, Helenius J. MD, PhD; Ophoff, Roel A. PhD; Fumoto, Katsumi PhD; Pasterkamp, R. Jeroen PhD; Dooijes, Dennis MD, PhD; Cuppen, Edwin PhD; Veldink, Jan H. MD, PhD; van den Berg, Leonard H. MD, PhD
[Article]
Archives of Neurology.
67(2):224-230, February 2010.
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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 (<36 months for 8 of 10 patients).
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.
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