Medline plus detailing SMN1 and SMN2 genes

Both of these genes detailed above code downstream for proteins that are needed for healthy development of motor neuron cells, specifically the anterior horn cells. SMN stands for Survival Motor Neuron and in individuals with SMA Spinal Muscular Atrophy the SMN1 gene is mutated. Generally the SMN2 gene copy number impacts the severity of the disease and the outcome of the different types of SMA. Type 0 and type 1 are the most severe types.

Mechanism of action from the same article is outlined and why it leads to SMA.

Researchers suggest that a shortage of SMN protein leads to the inefficient assembly of the machinery needed to process pre-mRNA. A lack of mature mRNA and subsequently, the proteins needed for normal cell functioning, has damaging effects on motor neuron development and survival. The loss of motor neurons leads to the signs and symptoms of spinal muscular atrophy. However, it is unclear why these cells are particularly sensitive to a reduction in the amount of SMN protein. Some research findings indicate that a shortage of SMN protein impairs the formation and function of axons and dendrites, leading to the death of motor neurons. While the mechanism is not clear, it is apparent that increased SMN2 gene copy number leads to an increase in SMN protein production, which improves the function and survival of motor neurons and results in less severe disease.

Source from medlineplus genetics page https://medlineplus.gov/genetics/gene/smn2/#conditions

Due to the lack of correctly working SMN protein, SMA individuals then experience muscular atrophy as signals are lost to the muscles which causes the symtoms seen in SMA. SMN2 shares only a single base pair difference with SMN1.

How do people inherit SMA ?

Healthy = 2 copies SMN1 (2 good copies of the gene)
Carrier = 1 copy of SMN1 (1 good copy and 1 mutated copy of the gene)

The disease is caused then when the child is born with no copies of SMN1.This happens when the child inhertis both mutated copies of SMN1 gene. There is also the SMN2 gene, which correlates with severity. SMN2 copy number is only of clinical relevance for the severity of SMA when SMN1 gene is mutated.

Carrier testing

Incidence is around 1:1000 births. In Ireland there are about 60,000 live births per year.

Approximately 1/40 to 1/50 people are SMA carriers in Ireland.
Thus, it is quite possible there are infants in Ireland missing this diagnosis.

For the reason above carrier-screening-for-spinal-muscular-atrophy is imperative as two individuals with the SMN1 mutation will have a 1 in 4 chance of a child with the disease.

SMA treatments

The prognosis is now much better since more is understood about the genetics of how this disease works.
Each year there is more research in the area and so it is expected more data and treatments will accumulate over time.

Breakthrough treatments for SMA