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Comparative Study
. 2015 Oct 15;10(10):e0139950.
doi: 10.1371/journal.pone.0139950. eCollection 2015.

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

Christian Czech  1 , Wakana Tang  2 , Teodorica Bugawan  2 , Calvin Mano  2 , Carsten Horn  1 , Victor Alejandro Iglesias  1 , Stefanie Fröhner  3 , Phillip G Zaworski  4 , Sergey Paushkin  5 , Karen Chen  5 , Thomas Kremer  1
Affiliations
Comparative Study

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

Christian Czech et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: CC, WT, TB, CM, CH, VAI, SF and TK are employees of F. Hoffmann-La Roche, LTD and its respective affiliates. PZ is an employees of Pharmoptima, INC. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Expression of SMN2 mRNA in SMA patients and healthy controls.
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.
Fig 2
Fig 2. SMN copy number determines expression of SMN in healthy subjects.
The copy number and the expression levels of SMN2 are closely linked; two copies show almost double expression of SMN2. Expression level is calculated using 2ˆ-deltaCp of the reference gene. Copy number is determined using digital PCR as described in Methods. Similar for SMN1, increases in copy number lead to increases in mRNA expression.
Fig 3
Fig 3. SMN2 copy numbers better predict the clinical phenotype than the expression level.
SMN protein was measured in whole blood using the SMN-ECL immunoassay as described. There is a large overlap between protein levels of the different disease Types, but there is a trend for protein increase depending on the copy number. Note that this could be confounded by age.
Fig 4
Fig 4. Correlation of protein and mRNA in SMA patients depend on Type.
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.
See this image and copyright information in PMC

References

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