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Decoding the Genetic Mysteries of Autosomal Recessive Amyotrophic Lateral Sclerosis 6

Medically reviewed by Brandon Colby, MD, last reviewed

Amyotrophic lateral sclerosis 6, autosomal recessive

Short answer: Amyotrophic lateral sclerosis 6 (ALS 6) is a form of ALS caused by variants in the FUS gene. The autosomal recessive form, which requires two altered copies, has been reported in only one family. Genetic testing of the FUS gene can help determine whether someone’s ALS is linked to this gene and help relatives understand their own risk.

Understanding Amyotrophic Lateral Sclerosis 6

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, the nerve cells in the brain and spinal cord that control voluntary muscle movement. As these cells are lost, people develop muscle weakness, stiffness, and wasting that can eventually affect speech, swallowing, and breathing. Most people with ALS have no known family history of the condition. About 5% to 10% of people with ALS have a family history of the disease. Changes in dozens of different genes have been linked to ALS.

ALS 6 is the name given to ALS caused by disease-causing variants in the FUS gene, often called FUS-ALS. Some people with FUS variants also develop frontotemporal dementia (FTD), which affects behavior, personality, and language. FUS-ALS often begins at a younger age than other forms of ALS. Disease-causing variants in FUS are the most commonly reported genetic cause of juvenile ALS, in which symptoms begin before age 25. FUS-ALS can progress quickly, although it varies from person to person.

The FUS Gene and How ALS 6 Is Inherited

The FUS gene, on chromosome 16, provides instructions for making a protein that binds RNA and helps process genetic messages inside the cell. Most ALS-causing FUS variants change the end of the protein that guides it into the cell nucleus. As a result, the protein can build up outside the nucleus and form clumps that may contribute to motor neuron damage.

In most families, ALS 6 follows an autosomal dominant inheritance pattern, meaning a harmful variant in just one copy of the FUS gene can cause the condition. Each child of a person with the variant has a 50% chance of inheriting it. FUS variants can arise for the first time in a person with no family history of ALS. These new, or de novo, variants are especially common in young-onset cases. The autosomal recessive form named in this article’s title is much rarer. It was reported in one family in which four affected relatives each had two copies of the same FUS variant, H517Q, with one copy inherited from each parent.

ALS-associated FUS variants are found in about 5% of people with familial ALS although estimates vary. Not everyone who carries an ALS-associated FUS variant develops the condition, and the age when symptoms begin can vary, even within the same family.

Diagnosing Amyotrophic Lateral Sclerosis 6

ALS is diagnosed by a neurologist based on symptoms, a neurological examination, and tests such as electromyography (EMG). Other tests help rule out conditions with similar symptoms. Genetic testing can identify an underlying genetic cause. Finding a disease-causing FUS variant in someone with ALS confirms FUS-ALS, rather than a form linked to another gene, such as SOD1, TARDBP, or C9orf72. Identifying the genetic cause can help guide treatment and determine eligibility for clinical trials of gene-targeted therapies.

Uses of Genetic Testing for Amyotrophic Lateral Sclerosis 6

Genetic testing for ALS 6 can be helpful in several ways:

  1. Confirming the Cause: For someone with ALS symptoms, identifying a FUS variant explains the cause of their condition and can guide conversations about care with their neurology team.
  2. Clinical Trial Eligibility: Gene-targeted trials for FUS-ALS enroll people based on their specific genetic result.
  3. Family Testing: Once a variant is found, relatives can choose whether to be tested. Testing people who do not have symptoms is a personal decision with emotional and practical implications, and it is best done with a genetic counselor.
  4. Family Planning: People who carry a disease-causing variant can discuss reproductive options, such as prenatal testing or preimplantation genetic testing, with a genetic counselor.

Related ALS Articles

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Frequently Asked Questions About ALS 6

What is ALS 6?

ALS 6 is a form of amyotrophic lateral sclerosis caused by variants in the FUS gene. Like other forms of ALS, it causes progressive loss of the motor neurons that control muscle movement. Some people with FUS variants also develop frontotemporal dementia.

Is ALS 6 inherited in a dominant or recessive pattern?

Most families with FUS-related ALS show autosomal dominant inheritance, where one altered copy of FUS can cause the condition. Autosomal recessive inheritance, which requires two altered copies, has been reported in only one family, which carried the FUS variant H517Q.

At what age does ALS 6 begin?

FUS-ALS often begins earlier than other forms of ALS, and FUS is the most common known genetic cause of juvenile ALS. It can also begin in middle or later adulthood.

How is ALS 6 diagnosed?

A neurologist diagnoses ALS from symptoms, a neurological exam, and tests such as electromyography (EMG). Genetic testing that finds a disease-causing FUS variant confirms that the ALS is FUS-related.

Should my relatives be tested?

If a FUS variant is found in your family, relatives can choose whether to be tested. Because results can carry significant emotional weight and not everyone with a variant develops ALS, it is best to talk with a genetic counselor before and after testing.

Does Sequencing test for this condition?

Whole genome sequencing reads 100% of your DNA, which includes the FUS gene and other genes linked to ALS. Sequencing's Kit Bundles include Next Gen Disease Screening, which analyzes your genome for more than 15,000 conditions. You can also upload DNA data from another test for free and search it in Genome Explorer. Results describe variants, not a diagnosis.

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References

  1. Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 2009;323(5918):1205-1208. doi:10.1126/science.1166066
  2. Vance C, Rogelj B, Hortobágyi T, et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 2009;323(5918):1208-1211. doi:10.1126/science.1165942
  3. Korobeynikov VA, Lyashchenko AK, Blanco-Redondo B, Jafar-Nejad P, Shneider NA. Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis. Nat Med. 2022;28(1):104-116. doi:10.1038/s41591-021-01615-z
  4. Ionis Pharmaceuticals. Ionis announces positive topline results from Phase 3 FUSION study of ulefnersen. Press release. September 22, 2026. https://ir.ionis.com/news-releases/news-release-details/ionis-announces-positive-topline-results-phase-3-fusion-study

This article is for education and is not a substitute for professional medical advice, diagnosis, or treatment. Talk to a qualified healthcare provider about your own health.