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Arch Neurol. 2010 Feb;67(2):224-30. doi: 10.1001/archneurol.2009.329.

FUS mutations in familial amyotrophic lateral sclerosis in the Netherlands.

Author information

1
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Heidelberglaan, Utrecht, the Netherlands.

Abstract

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.

PMID:
20142531
DOI:
10.1001/archneurol.2009.329
[Indexed for MEDLINE]

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