High Prevalence of SOD1 Pathogenic Variants in the UK Biobank: Implications for Early Intervention in Amyotrophic Lateral Sclerosis - PubMed
3 hours ago
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- #SOD1
- SOD1 is the second most frequently mutated gene in European ALS patients.
- Recent authorization of SOD1-targeted antisense oligonucleotides emphasizes the need for prompt SOD1 mutation screening in ALS patients.
- Analysis of 470,000 UK Biobank individuals identified 122 with monoallelic SOD1 variants, 93.4% asymptomatic.
- The low-penetrance p.Asp91Ala variant was found in 535 subjects, never in homozygosis.
- Expected SOD1-ALS prevalence is 1.04:100,000 in the UK, 4 times higher than clinically reported.
- Symptomatic carriers showed increased serum neurofilament levels at baseline.
- Age-related penetrance was higher in non-p.Asp91Ala carriers compared to p.Asp91Ala carriers.
- Long-term survival linked to p.Asp91Ala genotype, older age, and lower neurofilament levels.
- Incomplete penetrance and underascertainment likely explain the reduced number of symptomatic patients.
- Findings highlight the need to identify factors influencing disease penetrance and treatment response.