Abstract
Background:
SMN1 gene deletions cause spinal muscular atrophy, and SMN2 gene deletions have been associated with sporadic lower motor neuron diseases.
Objectives:
To study the frequency of abnormal SMN1 gene copy numbers and to determine whether SMN2 gene modulates the risk of amyotrophic lateral sclerosis (ALS) or the duration of evolution.
Method:
The authors studied SMN1 and SMN2 genes in 600 patients with sporadic ALS and 621 controls using a quantitative PCR method.
Results:
The authors found an association of ALS with an abnormal copy number (one or three copies) of SMN1 gene (p < 0.0001) with an OR of 2.8 (1.8 to 4.4, 95% CI). There was no association with SMN2 copy numbers and no effect of SMN2 copies on the duration of evolution in ALS independently of SMN1 copy number.
Conclusion:
Abnormal SMN1 gene copy numbers are a genetic risk factor in sporadic amyotrophic lateral sclerosis. There was no modulator effect of the SMN2 gene.
Publication types
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Controlled Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Amyotrophic Lateral Sclerosis / diagnosis
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Amyotrophic Lateral Sclerosis / epidemiology*
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Amyotrophic Lateral Sclerosis / genetics*
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Cyclic AMP Response Element-Binding Protein / genetics*
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DNA Mutational Analysis
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Female
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France / epidemiology
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Gene Dosage / genetics
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Genetic Predisposition to Disease / epidemiology
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Genetic Predisposition to Disease / genetics
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Genetic Testing / methods
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Humans
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Male
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Middle Aged
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Nerve Tissue Proteins / genetics*
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Prevalence
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RNA-Binding Proteins / genetics*
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Risk Assessment / methods*
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Risk Factors
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SMN Complex Proteins
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Survival of Motor Neuron 1 Protein
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Survival of Motor Neuron 2 Protein
Substances
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Cyclic AMP Response Element-Binding Protein
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Nerve Tissue Proteins
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RNA-Binding Proteins
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SMN Complex Proteins
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SMN1 protein, human
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SMN2 protein, human
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Survival of Motor Neuron 1 Protein
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Survival of Motor Neuron 2 Protein