SMN1

The SMN1 gene provides instructions for making a protein called SMN, which stands for "survival of motor neuron." The SMN protein is found throughout the body, with high levels in the spinal cord. This protein is particularly important for the survival 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). Healthy motor neurons are critical because they 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 a mature form. The SMN protein helps to assemble the cellular machinery needed to process pre-mRNA. The SMN protein may have additional functions in nerve cells. Research findings indicate that the SMN protein is important for the specialized outgrowths from nerve cells called dendrites and axons. Dendrites and axons are required for the transmission of impulses from nerve to nerve and from nerves to muscles.

spinal muscular atrophy - caused by mutations in the SMN1 gene

Normally, each cell has two copies of the SMN1 gene. About 95 percent of individuals with spinal muscular atrophy have mutations that delete all or some of the DNA in both copies of this gene. 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, and the other copy has a mutation that affects the building blocks (amino acids) used to make the SMN protein. Researchers have identified nearly 30 mutations that affect amino acids and impair the function of the SMN protein.

Although the SMN protein is found in cells throughout the body, it is unclear why motor neurons are particularly vulnerable to a shortage of this protein. Researchers suggest that a shortage of SMN protein leads to the inefficient assembly of the machinery needed to process pre-mRNA. Without mature mRNA, production of proteins necessary for cell growth and function is disrupted. Motor neurons may be particularly sensitive to this disruption, and these nerve cells die. Some research findings indicate that a shortage of SMN protein impairs the formation and function of axons and dendrites, which disturbs vital activities, and the nerve cells die. The loss of motor neurons leads to the signs and symptoms of spinal muscular atrophy.

In some cases of spinal muscular atrophy, particularly the milder cases, affected individuals have three or more copies of the SMN2 gene, which is almost identical to the SMN1 gene. On a limited basis, the protein produced by multiple copies of the SMN2 gene can help compensate for the reduced amount of SMN1 protein. 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 with 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. These studies found that people with amyotrophic lateral sclerosis were more likely to have only one copy or three copies of the SMN1 gene in each cell, instead of the usual two copies, compared with people unaffected by this disorder. An abnormal number of SMN1 genes alters the amount of SMN protein that is produced. Too little or too much SMN protein may impair the function of motor neurons, which increases the risk of developing amyotrophic lateral sclerosis.