Key result
PCR-based SMA newborn screening detects homozygous SMN1 deletions but misses compound heterozygous variants.
Why the study?
To evaluate the performance and limitations of a real-time polymerase chain reaction-based newborn screening assay for spinal muscular atrophy.
Does deletion-based newborn screening for SMA accurately detect patients with compound heterozygous SMN1 variants?
Observational (n=24)
Does deletion-based newborn screening for SMA accurately detect patients with compound heterozygous SMN1 variants?
Deletion-based newborn screening for SMA has an inherent false-negative limitation and cannot detect patients with compound heterozygous SMN1 variants.
Answers are grounded in this paper and cite their sources.
Deletion-based SMA newborn screening may miss compound heterozygous cases; leaves open need for variant-inclusive assays.
Newborn screening (NBS) facilitates the presymptomatic diagnosis and early treatment of spinal muscular atrophy (SMA). An analytical study was conducted to evaluate the performance and limitations of a real-time polymerase chain reaction-based SMA-NBS assay. Dried blood spot specimens collected from 21 newborns and three patients with genetically confirmed SMA were analyzed. The SMA controls included two patients with homozygous SMN1 deletion and one with compound heterozygous SMN1 variants. SMN1 exon 7 copy numbers were quantified and interpreted. All newborn participants had SMN1 copy numbers above the screening cutoff value of 668 copies/µL and were classified as screening-negative. The two SMA controls with homozygous SMN1 deletion showed no detectable SMN1 amplification, which is consistent with positive screening results. In contrast, the compound heterozygous SMA control exhibited a mean SMN1 value of 7330 copies/µL, which was more than tenfold above the screening cutoff and would therefore have been classified as screening-negative; this value also fell within the range observed in the newborn cohort. This patient had a negative NBS result at birth despite subsequently developing genetically confirmed SMA. The SMA-NBS assay accurately detected patients with homozygous SMN1 deletion. However, it did not identify patients with compound heterozygous SMN1 variants. In conclusion, deletion-based SMA-NBS has an inherent false-negative limitation, and a negative screening result does not completely exclude an SMA diagnosis.
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Abe et al. (2026) conducted an observational in Spinal muscular atrophy (SMA) (n=24). Real-time polymerase chain reaction-based SMA-NBS assay (deletion-based newborn screening) was evaluated on Detection of SMN1 copy numbers and screening classification. A real-time PCR-based newborn screening assay for SMA accurately detected homozygous SMN1 deletions but yielded a false-negative result for a patient with compound heterozygous SMN1 variants.
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