Biomarker for Spinal Muscular Atrophy: Expression of SMN in Peripheral Blood of SMA Patients and Healthy Controls

<div><p>Spinal muscular atrophy is caused by a functional deletion of SMN1 on Chromosome 5, which leads to a progressive loss of motor function in affected patients. SMA patients have at least one copy of a similar gene, SMN2, which produces functional SMN protein, although in reduced quantities. The severity of SMA is variable, partially due to differences in SMN2 copy numbers. Here, we report the results of a biomarker study characterizing SMA patients of varying disease severity. SMN copy number, mRNA and Protein levels in whole blood of patients were measured and compared against a cohort of healthy controls. The results show differential regulation of expression of SMN2 in peripheral blood between patients and healthy subjects.</p></div

Demographics of Enrolled SMA Patients.

<p>*<i>SMN2</i> copy number as reported by the patient and/or measured during the study. Copy number could not be determined for every patient.</p><p>Demographics of Enrolled SMA Patients.</p

Expression of SMN2 mRNA in SMA patients and healthy controls.

<p>SMN2 mRNA was isolated from blood and analyzed using qRT-PCR. Expression level is calculated using 2ˆ-deltaCp of the reference gene. There is a strong overlap of SMN2 mRNA in the different patient groups. Note that in the healthy controls SMN2 levels are lower than levels in patients with the same SMN2 copy number.</p

Correlation of protein and mRNA in SMA patients depend on Type.

<p>Significant correlation between expression levels of SMN protein and SMN2 mRNA in Type 1 and Type 2 patients but not in Type 3. Statistical analysis was done using Matlab 7.12. Protein levels are in ng/ml (x-axis) and mRNA (y-axis) Expression levels are calculated using 2ˆ-deltaCp of the reference gene.</p