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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hdl_62699.pdf | Published version | 727.56 kB | Adobe PDF | View/Open |
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