ALS is a rare, fatal, neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord.1 Onset of ALS is usually between the ages of 40 to 70, with the average age at diagnosis being 55 years. Unfortunately, typical life expectancy following diagnosis is only 3 to 5 years.1,2 ALS is a complex disease likely underpinned by the presence of different pathogenic mechanisms, including multiple genetic factors.2
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The discovery and investigation of these genes hold great promise for a better understanding of genetic ALS and disease management in the future.
SOD1 (superoxide dismutase 1) was the first gene discovered to be associated with ALS, identified in 1993.9 SOD1 accounts for approximately 15% of fALS patients and has been found in ~1% of sALS patients.10 C9orf72 (chromosome 9 open reading frame 72), discovered in 2011,7 accounts for approximately 33% of identified fALS patients and has been found to account for ~5% of sALS patients.10 These 2 genes are the most common gene mutations in genetic ALS, but there are many others, including TARDBP (~3.3% for fALS and ~0.5% for sALS), and FUS (~3.0% for fALS and ~0.4% for sALS).*10,11
*based on global population data.
Whole-genome or exome sequencing technology has assisted researchers in identifying more than 25 genes associated with familial ALS cases.2
Estimates of percentages are from European sources.
Although genetic testing is often limited to patients with a family history of ALS, research shows ~10% of sporadic ALS may have a genetic cause.6,12
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Genetic testing for all ALS patients may help provide a better understanding of the basis of their condition, allowing accurate risk assessment and a more comprehensive healthcare decisions and life choices.8 Clinical trials specific to genetic forms of ALS offer a reason to discover which ALS-associated mutation(s) a patient may carry.
Even though the percentage of sALS cases with a genetic component is smaller than fALS cases (approximately 10% of sALS cases compared to ~70% of fALS cases), their total number may account for the majority of ALS cases associated with genetic causation. This is because sALS cases make up about 90-95% of all ALS cases.4–7
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