Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/62699
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Type: Journal article
Title: FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis
Author: Blair, I.
Williams, K.
Warraich, S.
Durnall, J.
Theong, A.
Manavis, J.
Blumbergs, P.
Vucic, S.
Kiernan, M.
Nicholson, G.
Citation: Journal of Neurology, Neurosurgery and Psychiatry, 2010; 81(6):639-645
Publisher: British Med Journal Publ Group
Issue Date: 2010
ISSN: 0022-3050
1468-330X
Statement of
Responsibility: 
Ian P Blair, Kelly L Williams, Sadaf T Warraich, Jennifer C Durnall, Annora D Thoeng, Jim Manavis, Peter C Blumbergs, Steve Vucic, Matthew C Kiernan, Garth A Nicholson
Abstract: Objective: FUS gene mutations were recently identified in familial amyotrophic lateral sclerosis (ALS). The present studies sought to define the clinical, post-mortem and neurophysiological phenotypes in ALS families with FUS mutations and to determine the frequency of FUS mutations in familial and sporadic ALS. Methods: FUS was screened for mutations in familial and sporadic ALS cases. Clinical, post-mortem and neurophysiological features of large families with FUS mutations are described. Results and conclusions: FUS mutations were evident in 3.2% (4/124) of familial ALS, representing the second most common gene abnormality to be described in familial ALS after SOD1. No mutations were present in 247 sporadic ALS cases. The clinical presentation in 49 affected patients was consistent with a predominantly lower motor neuron disorder, supported by post-mortem findings. Upper motor neuron involvement varied, with Wallerian degeneration of corticospinal tracts present in one post-mortem case but absent in a second case from the same family. Features of cortical hyperexcitability demonstrated upper motor neuron involvement consistent with other forms of familial and sporadic ALS. One case presented with frontotemporal dementia (FTD) indicating that this may be a rare presenting feature in families with FUS mutation. Ubiquitin-positive cytoplasmic skein-like inclusions were present in lower motor neurons, but in contrast to sporadic ALS, no TDP-43 pathology was evident. Mutation-specific clinical features were identified. Patients with a R521C mutation were significantly more likely to develop disease at a younger age, and dropped-head syndrome was a frequent feature. Reduced disease penetrance was evident among most affected families.
Keywords: Brain
Humans
Amyotrophic Lateral Sclerosis
Ribonuclease, Pancreatic
Superoxide Dismutase
RNA-Binding Protein FUS
Microtubule-Associated Proteins
DNA-Binding Proteins
Vesicular Transport Proteins
Nerve Tissue Proteins
RNA, Messenger
Severity of Illness Index
DNA Mutational Analysis
Cognition Disorders
Neuropsychological Tests
Point Mutation
Adult
Aged
Middle Aged
Female
Male
Young Adult
Genetic Testing
Endosomal Sorting Complexes Required for Transport
Dynactin Complex
Superoxide Dismutase-1
Rights: Copyright © The Authors
DOI: 10.1136/jnnp.2009.194399
Published version: http://dx.doi.org/10.1136/jnnp.2009.194399
Appears in Collections:Aurora harvest
Pathology publications

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