A method for the diagnosis of spinal muscular atrophy (SMA) and the quantification of SMN1 and SMN2 gene copies is described in an article published in Clinica Chimica Acta.

The new assay, called MS-CNV, combines real competitive polymerase chain reaction (PCR) with matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy to quantify gene copy numbers of the SMN1 and SMN2 genes to help facilitate the screening of carriers and the diagnosis of SMA. Gene copy quantification can also help identify treatments that may be suitable for the patient.

MS-CNV also quantifies the copies of the nearby NAIP gene, which has been previously suggested as a protective factor for SMA.

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“MS-CNV can be used for carrier screening and genetic diagnosis of SMA, providing dosages information for both SMN1 and SMN2 given its accuracy and high sample processing throughput by mass spectrometric analysis,” the authors said.

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During the study, MS-CNV was found to give consistent results when compared to multiplex ligation-dependent probe amplification (MLPA) in 2 different cohorts containing patients with SMA, SMA carriers, and healthy volunteers. The first cohort contained 3 patients with SMA, 5 carriers, and 71 volunteers with unknown SMA genetic information. MS-CNV and MLPA both correctly identified the 3 SMA patients and 5 carriers. An additional 3 carriers were identified by both methods in a group of volunteers with unknown SMA status.

In the second cohort, a blinded set of 62 blood samples from unknown numbers of SMA patients, carriers, and healthy volunteers was analyzed by both MS-CNV and MLPA. The MS-CNV method identified 21 patients with SMA, 14 carriers, and 27 healthy cases, which were consistent with the MLPA results.

The full assay time for MS-CNV was around 6.5 to 7 hours, which included PCR, and shrimp alkaline phosphatase treatment to remove excess deoxyribonucleotide triphosphates, single base extension, mass spectrometry, and data analysis. This is a significant improvement in both hands-on and overall time compared to MLPA, the authors concluded.


Jin W, Yang Z, Tang X, et al. Simultaneous quantification of SMN1 and SMN2 copy numbers by MALDI-TOF mass spectrometry for spinal muscular atrophy genetic testing. Clin Chim Acta. Published online May 26, 2022. doi:10.1016/j.cca.2022.05.017