From validation to application: implementing a cost-effective QPCR assay for presymptomatic and symptomatic SMA diagnosis [Articol]

Abstract

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused mainly by homozygous deletion of exon 7 in the SMN1 gene. Early qualitative and quantitative diagnosis, especially in the presymptomatic stage, is essential for timely access to treatment and improved outcomes. This study focused on developing and implementing a sensitive, rapid, and cost-effective real-time PCR-based method for detecting the exon 7 deletion in SMN1. The test was first validated using 25 clinical samples, then applied in a pilot study on 300 dried blood spot samples to assess its use in presymptomatic newborn screening. The method demonstrated high sensitivity and specificity, a fast turnaround time, and suitability for both symptomatic and presymptomatic diagnosis. Compared to commercial alternatives, the custom assay proved more cost-efficient while maintaining diagnostic reliability. Despite challenges such as lack of national protocols, ethical considerations, and logistical constraints, the findings support integrating this method into routine diagnostics. Its implementation highlights the need for structured policies and infrastructure to enable equitable access to genetic screening for rare diseases like SMA.