Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by the loss of motor neurons, which leads to progressive muscle weakness and atrophy. The condition is directly linked to mutations in a specific gene known as Survival of Motor Neuron 1, or SMN1. Understanding the function of this gene is fundamental to comprehending how SMA develops.
What Is the SMN1 Gene?
The SMN1 gene provides the primary instructions for producing a protein called Survival of Motor Neuron (SMN). This protein is found throughout the body and is necessary for the maintenance and function of all cells. It is particularly important for a specific type of nerve cell called a motor neuron.
Motor neurons are located in the spinal cord and brainstem and are responsible for transmitting signals from the brain to the muscles, controlling voluntary movements like walking, speaking, and breathing. The SMN protein plays a direct role in the survival of these neurons. Without a sufficient supply of this protein, motor neurons begin to shrink and die, disrupting communication between the brain and muscles.
The Role of the SMN2 Gene
Humans have a nearly identical backup gene called SMN2. While structurally similar to SMN1, a small difference in its genetic code causes it to produce significantly less functional SMN protein. Most of the protein made from the SMN2 gene is short-lived and quickly degraded.
Although it is less efficient, the SMN2 gene can still produce a small amount of the full-length SMN protein. The number of SMN2 copies an individual has can vary, and this number often influences the severity of SMA in people who lack a functional SMN1 gene. More copies of SMN2 generally lead to a milder form of the disorder because more functional protein is available.
How SMN1 Mutations Cause SMA
SMA is an autosomal recessive disorder, which means an individual must inherit two non-functional copies of the SMN1 gene—one from each parent—to develop the condition. The most common cause of a non-functional SMN1 gene is a deletion, where a segment of the gene is missing entirely.
When both copies of the SMN1 gene are absent or mutated, the body cannot produce the required amount of SMN protein. It must then rely entirely on the less effective SMN2 gene. The resulting protein deficiency leads to the progressive loss of motor neurons, causing the muscle weakness and atrophy that define SMA.
Types of Spinal Muscular Atrophy
SMA is classified into different types based on the age of onset and the highest physical milestone achieved by the patient. The classification helps in understanding the prognosis and guiding management. The severity of the disease often correlates with the number of SMN2 gene copies a person has.
- Type 0 is the most severe form, with symptoms appearing before birth, including reduced fetal movement.
- Type I has an onset within the first six months of life, and affected infants are unable to sit without support.
- Type II becomes apparent between 6 and 18 months of age; children can often sit but cannot stand or walk independently.
- Type III is a milder form with an onset after 18 months, where individuals can initially walk but may lose the ability over time.
- Type IV is the mildest form, with symptoms typically beginning in adulthood and progressing slowly.
Genetic Testing and Carrier Screening
Genetic testing is the definitive method for diagnosing SMA. A blood test can identify the deletion or mutation in both copies of the SMN1 gene. This testing can also determine the number of SMN2 copies an individual possesses, which provides insight into the potential severity of the disease.
Carrier screening is also available for individuals who want to know if they carry a non-functional copy of the SMN1 gene. Carriers do not have symptoms of SMA but can pass the mutated gene to their children. This screening is particularly relevant for prospective parents with a family history of the disorder, as it helps them understand the risk of having a child with SMA.