SMA (Spinal Muscular Atrophy), SMN1 Gene
Definition
A neuromuscular disease inherited in an autosomal recessive manner, characterized by degeneration of the motor neurons in the spinal cord due to loss of the SMN1 gene.
Why it is examined by copy number analysis rather than sequencing:
SMN1 and SMN2 share more than 99% nucleotide identity, with only 8 nucleotide differences between them. For this reason standard DNA sequencing cannot reliably distinguish the two genes from each other. Gene-targeted deletion/duplication analysis is required to determine the SMN1 dosage.
This is the explanation of why SMA is analyzed separately in the carrier screening panel (see the Carrier Screening Panel entry).
Carrier frequency (by population):
| Population | Frequency |
|---|---|
| White | 1/45 |
| Asian | 1/48 |
| Hispanic | 1/77 |
| Black (sub-Saharan African) | 1/100 |
The role of SMN2 copy number: The SMN2 gene produces a small amount of functional protein and can partially compensate for the loss of SMN1. For this reason the SMN2 copy number is used to predict the severity of the disease:
| SMN2 copy number | Prediction |
|---|---|
| 2 copies | ~80% probability of SMA type I (the most severe form) |
| 4 or more | ~88% probability of a milder course, ability to walk |
Risks and Limitations
Copy number analysis cannot detect point mutations within SMN1; in a small proportion of carriers (about 5%) the test may be negative (residual risk).