What an SMN1 Deletion Means for Motor Neuron Health

The human body is built and maintained by a vast set of genetic instructions called genes. These genes provide the blueprints for proteins, the molecules that perform a wide array of tasks within our cells. One of these, the Survival Motor Neuron 1 (SMN1) gene, holds a specific role in the nervous system. When a portion of this genetic code is lost—an event known as a gene deletion—the cell can no longer properly read the instructions it contains. This disrupts the production of its corresponding protein and can significantly affect the body’s function.

Understanding the SMN1 Gene’s Role

The primary function of the SMN1 gene is to provide instructions for producing the Survival Motor Neuron (SMN) protein. While found throughout the body, this protein is most concentrated within the spinal cord. The SMN protein is part of a larger complex that helps create and maintain specialized nerve cells known as motor neurons, which are located in the brainstem and spinal cord.

Motor neurons are the communication lines between the central nervous system and the body’s skeletal muscles. They transmit electrical signals from the brain that command muscles to contract, enabling voluntary movements like walking, talking, breathing, and swallowing. The SMN protein is important for the health and survival of these motor neurons, and without sufficient amounts, these nerve cells cannot function correctly.

Consequences of SMN1 Gene Deletion

The complete loss of both copies of the SMN1 gene, known as a homozygous deletion, is the primary cause of the genetic disorder Spinal Muscular Atrophy (SMA). Occurring in about 1 in 10,000 live births, SMA is a progressive neurodegenerative disease that targets motor neurons.

As a result, motor neurons in the spinal cord and brainstem deteriorate and die. This loss disrupts the signaling pathway between the brain and muscles, which no longer receive commands to move. This leads to progressive muscle weakness and atrophy (the wasting away of muscle tissue). Symptoms of SMA can include difficulty with motor skills like sitting and walking, as well as challenges with breathing and swallowing.

The Modifying Influence of the SMN2 Gene

Humans have a second, nearly identical gene called SMN2, often called a “backup” to SMN1. While SMN2 also produces the SMN protein, a subtle genetic difference causes most of its output to be a shorter, unstable version that is not fully functional. Only about 10-15% of the protein from SMN2 is the full-length version that can support motor neurons.

This small amount of protein is not enough to completely compensate for the loss of SMN1. However, the number of SMN2 copies an individual has can influence the severity of SMA. A higher number of SMN2 copies leads to more functional SMN protein, which often results in a milder form of the disease with a later onset of symptoms.

Inheritance Patterns of SMN1 Deletion

Spinal Muscular Atrophy from an SMN1 deletion is inherited in an autosomal recessive pattern. This means an individual must inherit two non-functional copies of the gene—one from each parent—to be affected. The term “autosomal” indicates the gene is on a numbered chromosome, not a sex chromosome.

Individuals who inherit one functional and one non-functional SMN1 gene are known as carriers. They produce enough SMN protein from their single working copy to remain healthy and show no symptoms. Carriers can, however, pass the non-functional gene to their children. When two carriers have a child, there is a 25% chance the child will have SMA, a 50% chance the child will be a carrier, and a 25% chance the child will be unaffected.

Diagnostic Processes and Therapeutic Options

The diagnosis of SMA is confirmed through genetic testing, most commonly a molecular test on a blood sample. This test looks for the homozygous deletion of a segment in the SMN1 gene, found in over 95% of cases. In many regions, newborn screening programs now test for SMN1 deletions, allowing for diagnosis before symptoms appear, which is important for initiating early treatment.

Several treatments are now available that address the underlying genetic cause of SMA. One approach is gene replacement therapy, which delivers a new, functional copy of the SMN1 gene to cells. Another strategy involves therapies that modify the SMN2 gene to increase its production of full-length, functional SMN protein. These treatments help to slow or halt the progression of the disease by restoring the body’s ability to support its motor neurons.