Researchers discovered that a real-time polymerase chain reaction (PCR) test based on high-resolution melting offered a high-throughput and advantageous approach to large-scale screening for spinal muscular atrophy (SMA) and published their findings in Brain & Development.

Alterations in the SMN1 gene are the main drivers of SMA pathology. Research indicates that the overwhelming majority of patients with SMA (more than 90%) have a homozygous deletion of the SMN1 gene. The prevalence of SMA is approximately 1 in 6000 to 10,000 live births.

“Considering the potentially severe phenotype and the extraordinary prevalence of SMA, the American College of Medical Genetics and Genomics recommends population-wide SMA screening,” the authors wrote.


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Research indicates that high-resolution melting analysis is a potent post-PCR technique that simplifies operational steps and reduces detection costs. Hence, this approach may be suitable for large-scale population screening. One of the best approaches to this is to screen for the copy number of SMN1, the authors said. Simultaneously, carrier testing can be carried out in the preconception or prenatal period.

To test this screening approach for SMA, the research team recruited 2563 individuals who were either confirmed patients with SMA, suspected cases, as well as individuals from the general population. They were then tested for SMA using real-time PCR with high-resolution melting. The results were then compared with the multiplex ligation-dependent probe amplification (MLPA) test. 

The results revealed 10.18% detection of homozygous deletions and 2.26% detection of heterozygous deletions using the real-time PCR with the high-resolution melting method. Statistical analysis demonstrates that this approach had high reproducibility and concordance with MLPA.

“The assay in general can be used for large-scale SMA carrier screening as a highly-sensitive and high-throughput way with low cost and labor,” the authors concluded. This means that both parents and physicians can make informed decisions and start treatment early.

Reference

Xu Y, Song T, Wang X, et al. Copy number assessment of SMN1 based on real-time PCR with high-resolution melting: fast and highly reliable testingBrain Dev. Published online April 9, 2022. doi:10.1016/j.braindev.2022.03.011