SMN1

The SMN1 gene provides instructions for making the survival motor neuron (SMN) protein. The SMN protein is found throughout the body, with high levels in the spinal cord. This protein is particularly important for the maintenance of specialized nerve cells called motor neurons, which are located in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). Motor neurons control muscle movement.

In cells, the SMN protein plays an important role in processing molecules called messenger RNA (mRNA), which serve as genetic blueprints for making proteins. Messenger RNA begins as a rough draft (pre-mRNA) and goes through several processing steps to become a final, mature form. The SMN protein helps to assemble the cellular machinery needed to process pre-mRNA. Research findings indicate that the SMN protein is also important for the development of specialized outgrowths from nerve cells called dendrites and axons. Dendrites and axons are required for the transmission of impulses between nerves and from nerves to muscles.

A small amount of SMN protein is produced from a gene similar to SMN1 called SMN2. The SMN2 gene provides instructions for making several versions of the SMN protein, but only one version is functional; the other versions are smaller and easily broken down.

spinal muscular atrophy - caused by mutations in the SMN1 gene

About 95 percent of individuals with spinal muscular atrophy have mutations that delete a section called exon 7 in both copies of the SMN1 gene in each cell. As a result, little or no SMN protein is made. In about 5 percent of people with this disorder, one copy of the SMN1 gene has a deletion of exon 7, and the other copy has a different mutation that disrupts the production or function of the SMN protein. Researchers have identified at least 65 mutations in the SMN1 gene that cause spinal muscular atrophy.

Motor neurons seem to be particularly vulnerable to a shortage of the SMN protein and die prematurely. Researchers suggest that a shortage of SMN protein leads to the inefficient assembly of the machinery needed to process pre-mRNA. Without mature mRNA, the production of proteins necessary for cell growth and function is disrupted. Some research findings indicate that a shortage of SMN protein impairs the formation and function of axons and dendrites, possibly leading to the death of neurons. While the cause of neuronal death is unclear, it is the loss of motor neurons that leads to the signs and symptoms of spinal muscular atrophy.

In some cases of spinal muscular atrophy, in addition to their SMN1 gene mutations, affected individuals have three or more copies of the SMN2 gene in each cell. Extra SMN2 genes can help replace some of the SMN protein that is lost due to mutations in the SMN1 genes. In general, symptoms are less severe and begin later in life in affected individuals with three or more copies of the SMN2 gene compared with those who have two copies of the gene.

amyotrophic lateral sclerosis - increased risk from variations of the SMN1 gene

Some studies suggest that an abnormal number of SMN1 genes in each cell may be associated with an increased risk of developing amyotrophic lateral sclerosis (ALS), a condition characterized by progressive movement problems and muscle wasting. People with ALS are more likely to have three copies of the SMN1 gene in each cell, whereas people without the condition normally have two copies of the gene. The presence of extra SMN1 genes increases the amount of SMN protein that is produced. Too much SMN protein may impair the function of motor neurons, which increases the risk of developing ALS.