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ALS - Motor Neuron Disease: Mechanism and Development of New Therapies
Published on: July 29, 2007
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Genetic characterization of primary lateral sclerosis.
Eva M J de Boer1, Balint S de Vries1, Maartje Pennings2
1Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Journal of Neurology
|May 3, 2023
Summary
Genetic analysis in primary lateral sclerosis (PLS) identified pathogenic variants in 7% of patients, predominantly linked to amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP). This suggests genetic testing aids PLS diagnosis.
Area of Science:
- Neurogenetics
- Motor Neuron Diseases
Background:
- Primary lateral sclerosis (PLS) is a rare motor neuron disease characterized by upper motor neuron degeneration.
- Distinguishing PLS from amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP) is clinically challenging.
- Current diagnostic guidelines recommend against extensive genetic testing due to limited data.
Purpose of the Study:
- To genetically characterize a cohort of PLS patients.
- To identify genetic variants associated with PLS and related motor neuron diseases.
- To evaluate the utility of genetic testing in the diagnostic work-up for PLS.
Main Methods:
- Whole exome sequencing (WES) was performed on 139 PLS patients.
- Analysis included genes associated with ALS, HSP, ataxia, and movement disorders (364 genes).
- C9orf72 repeat expansions were analyzed separately in 129 patients.
Main Results:
- Genetic analysis identified 31 variants in 139 PLS patients (22%).
- Eleven variants (7%) were classified as (likely) pathogenic.
- Pathogenic variants were associated with ALS-Frontotemporal Dementia (ALS-FTD), pure HSP, and an ALS-HSP-CMT overlap.
Conclusions:
- Genetic analyses revealed pathogenic variants in a significant portion of the PLS cohort.
- These variants link PLS to other neurodegenerative conditions like ALS and HSP.
- Genetic testing should be considered in the diagnostic evaluation of primary lateral sclerosis.
