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Is ALS Genetic?

Amyotrophic lateral sclerosis (ALS) has been the object of medical research for many years. One of the most frequently asked questions concerning this disease is whether ALS is genetic. This article will discuss the possible genetic components of ALS. 

Familial vs. Sporadic ALS

ALS can be broadly classified into two categories based on its origin: familial ALS (FALS) and sporadic ALS (SALS).

  • Familial ALS: About 5-10% of all ALS cases are familial. In these cases, the disease runs in families and is caused by mutations in specific genes, and carried on. If one family member is diagnosed with FALS, the risk of other family members developing the disease significantly increases.
  • Sporadic ALS: About 90-95% of ALS cases are sporadic. This means that they occur randomly without any clear familial pattern. While the exact cause of SALS is still not entirely known, current research has suggested that its etiology lies somewhere in a combination of genetic and environmental factors. 

The Role of Genetics

Genetic mapping has identified multiple genes concerning FALS. Some of the most significant include:

  1. C9ORF72: A mutation in this gene is the most common genetic cause of FALS and is found in about 25-40% of familial cases.
  2. SOD1: Mutations in the SOD1 gene account for around 20% of FALS cases.
  3. TARDBP and FUS: These genes are less commonly associated with FALS but have been identified in a smaller percentage of patients.

Some research has shown that these mutations are not only linked to FALS, as they have also been found in a very small number of SALS patients, suggesting that genetics can play a role even in sporadic cases.

Genetic Testing and Counseling

Families with a history of ALS are suggested to undergo genetic testing to identify known ALS-associated mutations. 

 It's crucial to undergo genetic counseling before and after testing to understand the potential results. 

While a portion of ALS cases are genetic, particularly in familial instances, the majority of cases are sporadic and may arise from a combination of several factors. You can read more about the possible causes of ALS here

Amyotrophic Lateral Sclerosis (ALS)
C9ORF72: What It Is, What It Does, and Why It Matters
SOD1 in ALS: Taking Stock in Pathogenic Mechanisms and the Role of Glial and Muscle Cells
TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis

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