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Articles
December 1, 1997

Familial amyotrophic lateral sclerosis
Molecular pathology of a patient with a SOD1 mutation

December 1997 issue
49 (6) 1612-1616

Abstract

We report the clinical, genetic, and neuropathologic findings in a patient with rapidly progressive familial amyotrophic lateral sclerosis (ALS). We detected a point mutation at codon 48 of the Cu/Zn superoxide dismutase gene(SOD1) leading to a substitution of histidine by glutamine in the copper-binding domain. The histopathologic features are consistent with those described in rapidly progressive sporadic ALS and do not support claims that sporadic and familial disease are different pathologic entities. Neurofilamentous accumulations, hyaline, and ubiquitinated inclusions were present in the motor cortex, brainstem, and anterior horn cells, but there was no evidence of abnormal SOD1 immunoreactivity. This confirms that the cytoskeletal pathology specific to ALS is secondary to an unknown biochemical disturbance caused by mutant SOD1 molecules and not its toxic accumulation.

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Information & Authors

Information

Published In

Neurology®
Volume 49Number 6December 1997
Pages: 1612-1616
PubMed: 9409355

Publication History

Published online: December 1, 1997
Published in print: December 1997

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Authors

Affiliations & Disclosures

C. E. Shaw, FRACP
From the Department of Clinical Neurosciences, Institute of Psychiatry and Kings College School of Medicine and Dentistry (Drs. Leigh, Shaw, and Radunovic, and Z.E. Enayat and V.E.R. Anderson); the Department of Neuroscience (Dr. Powell) and the Department of Neuropathology (Dr. Al-Sarraj), Institute of Psychiatry, London, UK.
Z. E. Enayat, MSc
From the Department of Clinical Neurosciences, Institute of Psychiatry and Kings College School of Medicine and Dentistry (Drs. Leigh, Shaw, and Radunovic, and Z.E. Enayat and V.E.R. Anderson); the Department of Neuroscience (Dr. Powell) and the Department of Neuropathology (Dr. Al-Sarraj), Institute of Psychiatry, London, UK.
J. F. Powell, PhD
From the Department of Clinical Neurosciences, Institute of Psychiatry and Kings College School of Medicine and Dentistry (Drs. Leigh, Shaw, and Radunovic, and Z.E. Enayat and V.E.R. Anderson); the Department of Neuroscience (Dr. Powell) and the Department of Neuropathology (Dr. Al-Sarraj), Institute of Psychiatry, London, UK.
V.E.R. Anderson, MSc
From the Department of Clinical Neurosciences, Institute of Psychiatry and Kings College School of Medicine and Dentistry (Drs. Leigh, Shaw, and Radunovic, and Z.E. Enayat and V.E.R. Anderson); the Department of Neuroscience (Dr. Powell) and the Department of Neuropathology (Dr. Al-Sarraj), Institute of Psychiatry, London, UK.
A. Radunovic, MD, PhD
From the Department of Clinical Neurosciences, Institute of Psychiatry and Kings College School of Medicine and Dentistry (Drs. Leigh, Shaw, and Radunovic, and Z.E. Enayat and V.E.R. Anderson); the Department of Neuroscience (Dr. Powell) and the Department of Neuropathology (Dr. Al-Sarraj), Institute of Psychiatry, London, UK.
S. Al-Sarraj, MSc, MRCPath
From the Department of Clinical Neurosciences, Institute of Psychiatry and Kings College School of Medicine and Dentistry (Drs. Leigh, Shaw, and Radunovic, and Z.E. Enayat and V.E.R. Anderson); the Department of Neuroscience (Dr. Powell) and the Department of Neuropathology (Dr. Al-Sarraj), Institute of Psychiatry, London, UK.
P. N. Leigh, PhD, FRCP
From the Department of Clinical Neurosciences, Institute of Psychiatry and Kings College School of Medicine and Dentistry (Drs. Leigh, Shaw, and Radunovic, and Z.E. Enayat and V.E.R. Anderson); the Department of Neuroscience (Dr. Powell) and the Department of Neuropathology (Dr. Al-Sarraj), Institute of Psychiatry, London, UK.

Notes

Address correspondence and reprint requests to Dr Shaw, Department of Clinical Neuroscience, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.

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