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Updated: May 2, 2026
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Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
Published on: July 16, 2021
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FXN GAA repeat expansions in amyotrophic lateral sclerosis
Naji Rizik1, Axel Freischmidt1, Albert C Ludolph1
1Department of Neurology, Ulm University, Albert-Einstein-Allee 11, Ulm 89081, Germany.
Summary
Heterozygous trinucleotide expansion in the frataxin (FXN) gene was investigated as a risk factor for amyotrophic lateral sclerosis (ALS). This study found no evidence that FXN expansion modifies ALS risk or phenotype, supporting distinct mechanisms for DNA repeat expansion toxicity.
Area of Science:
- Genetics
- Neuroscience
- Mitochondrial Biology
Background:
- Friedreich's ataxia is caused by homozygous trinucleotide expansions in the frataxin (FXN) gene.
- Heterozygous FXN expansion leads to reduced frataxin expression and a subclinical metabolic phenotype, suggesting potential broader implications.
Purpose of the Study:
- To investigate if heterozygous FXN trinucleotide expansion acts as a risk factor or modifier for amyotrophic lateral sclerosis (ALS).
Main Methods:
- Genomic DNA from 652 ALS patients (familial and sporadic) and 238 controls was analyzed.
- Polymerase chain reaction (PCR) was used to detect extended FXN trinucleotide repeats.
Main Results:
- The overall frequency of heterozygously extended FXN repeats in ALS patients was lower than anticipated.
- No significant difference in FXN expansion frequency or its effect on ALS disease phenotype was detected between patients and controls.
Conclusions:
- The findings do not support heterozygous FXN expansion as a risk factor or modifier for ALS.
- This reinforces the concept that distinct biological mechanisms underlie the toxicity of different DNA repeat expansions.
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