The ALS Association

ALS Ice Bucket Challenge Progress

Your Guide to Decoding ALS Genetics

insight-feb2015-dna-article

Although the most common form of ALS in the United States is “sporadic,” meaning the disease can strike anyone, at anytime, genetics play a role in about 5 to 10 percent of all cases of the disease. In most of those cases, another family member also has ALS or a related disease. Such cases of familial ALS (FALS) are presumed to be due to inherited genetic changes or mutations although the gene may not be known in all cases.

As scientific knowledge of this complicated disease continues to rapidly progress, it is predicted that even more cases of sporadic ALS will be attributed to genetic causes.

Known genes that cause ALS

C9org72
Discovered in 2011, this gene is now considered the most common genetic cause of ALS accounting for somewhere between 25 and 40 percent of all cases of familial ALS and approximately four to six percent of all sporadic cases. This gene has also been linked to other diseases including dementia and is presently the subject of intense research.

Cu/Zn Superoxide Dismutase (SOD1)
First discovered in 1993, this is the first gene known to cause ALS. It accounts for 10 percent of all cases of familial ALS and is present in 1.5 to 2 percent of all cases of the disease. More than 100 different mutations that alter an enzyme found inside human cells have been attributed to this complicated gene.

TDP-43
Linked to ALS in 2008, this gene causes important proteins found in the body’s motor neurons to essentially take up residence in a different area of the cell structure where they are not ordinarily found. It is suggested that these microscopic movements may play an important role in understanding many forms of ALS even when there is no clear genetic link.

Fused in Sarcoma (FUS)
Sharing similarities with the protein function of TDP-43, this gene was also discovered in 2008. It is likely that mutations in this gene prevent clearing the body’s cells of harmful protein material, thereby possibly leading to disease.

Valosin-containing Protein (VCP) and other genes
Other genetic causes of ALS affect relatively few people including VCP, alsin, senataxin, angiogenin, optineurin, FIG4 (polyphosphoinositide phosphatase), UBQLN2 (Ubiquilin-2), SPG20 (spartin) and VAPB (vesicle-associated membrane protein-associated protein B/C). Scientists believe understanding how these more rare genes cause ALS may lead to a better understanding of the disease process.

Gene Therapy: Hope on the Horizon

Relying upon an ever expanding knowledge of the role genes play in the onset and progression of ALS, scientists are hard at work to develop a gene therapy, which may save dying nerve cells and slow the disease.  

Gene therapy is still an experimental concept and is based on the knowledge that genes are present in all cells of the body and carry the instructions that form the building blocks of the human body. By producing genetic instructions to treat a mutated gene or cellular deficiency, doctors may one day be able to repair or even turn off the genes that cause ALS.

Scientists believe gene therapy may even be effective in treating those without a gene or mutation that causes ALS.

If you are interested in learning more about clinical trials where gene therapy may be the focus of study, talk with your health care provider or visit: http://www.alsconsortium.org/search.php

Is Genetic Testing Right for You?

Having a family history of ALS can increase anxiety, but it doesn’t necessarily mean a diagnosis is imminent. In about 90 percent of cases, the person with ALS is the only member of the family with the disease.

It is important to know that genetic testing cannot be used to diagnose ALS in people without symptoms. Testing is most useful in a person who has been diagnosed with ALS and is seeking help in determining the cause of FALS in their family.

Genetic testing is not for everyone. Some people at risk for FALS decline genetic testing to avoid worry knowing there is presently no cure for this disease. Others wish to avoid the guilt that can occur over passing the gene on to children or testing negative when others in the family may test positive.

Others choose to move forward with genetic testing to reduce their own anxiety and to feel better prepared to make plans for the future.

That is why it is important to work with a genetic counselor that can help you navigate the pros and cons of testing based on your unique concerns and values. To find a counselor in your area, visit: www.nsgc.org.

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