How does the number of SMN2 copies affect spinal muscular atrophy?

The number of SMN2 (Survival Motor Neuron 2) gene copies plays a crucial role in the severity of spinal muscular atrophy (SMA). In SMA, the survival motor neuron 1 (SMN1) gene is typically mutated or deleted, which leads to a deficiency in the SMN protein necessary for the survival of motor neurons. The SMN2 gene, which is a paralog of SMN1, can partially compensate for this loss because it produces some SMN protein, although it is often less effective due to alternative splicing.

Having more copies of the SMN2 gene results in an increased production of the SMN protein, which can mitigate the severity of the disease. Patients with a higher number of SMN2 copies generally experience milder forms of SMA and can maintain better motor function compared to those with fewer copies. Therefore, the relationship between SMN2 copy number and disease severity is significant; more copies lead to reduced severity of symptoms.

In contrast to this, having fewer SMN2 copies doesn’t result in normal health, as SMA is characterized by muscle weakness and atrophy due to inadequate levels of the SMN protein. Similarly, the notion that copy number has no effect on the disease and