Spinal muscular atrophy (SMA) is an inherited neuromuscular disease that leads to dysfunction and death of motor neurons, the nerve cells that cause muscles to contract. The loss of motor neurons causes the muscles they control to atrophy, or become smaller.
Mutation in the SMN1 gene causes most cases of SMA
Most cases of SMA are due to mutation in the SMN1 (survival of motor neuron) gene on chromosome 5. The mutant gene cannot produce its protein product, called SMN, which, as its name implies, is necessary for motor neuron survival.
This loss can be partially offset by the presence of neighboring SMN2 genes, which are similar in structure to SMN1 genes. However, SMN2 genes lack a single DNA “letter,” which causes loss of one section (exon 7) of the messenger RNA made from the SMN2 gene. Because of this, most (though not all) of the protein made from SMN2 genes is short and not functional.
The number of SMN2 genes varies from person to person. In chromosome 5-related SMA, the more copies of the SMN2 gene that a person has, the more functional SMN protein is available, the later the onset of disease symptoms, and the milder the disease course is likely to be.
There are also other forms of SMA that are not related to a deficiency of SMN protein, arising instead from defects in different genes on different chromosomes.
Because most cases of SMA are due to SMN1 mutation, most treatment research has focused on this form of the disease. Strategies include increasing the amount of SMN protein produced from the SMN2 gene, correcting the gene mutation in SMN1, and protecting motor neurons from the consequences of loss of SMN.