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Novel Screening Method Shows Promise in Detecting SMA


Researchers have developed a new line method (NLM) that showcased benefits for genetic screening in spinal muscular atrophy (SMA).

A new line method (NLM) as a direct real-time PCR test procedure without nucleic acid extraction in dried blood spots (DBS) showed promise for detecting the homozygous deletion of exon 7 of the survival motor neuron 1 (SMN1) gene in patients with spinal muscular atrophy (SMA), according to a study published in Molecular Genetics & Genomic Medicine.

In the last decade, treatment options for spinal muscular atrophy (SMA) have become available and shown great benefits; however, their effectiveness depends on how early treatment can begin before the onset of symptoms. This urgency is especially true in SMA type 1, where motor neurons and functions can begin drastically deteriorating at just 3 months of age. Fortunately, nucleic acid-based assays have given clinicians a proper tool for early screening and detection of genetic diseases such as SMA.

PCR loading | image credit: angellodeco - stock.adobe.come

PCR loading | image credit: angellodeco - stock.adobe.come

The authors mention a number of hurdles that accompany testing for SMA in the dried blood spot (DBS) samples of newborns, including DNA extraction, the tracking and recording of the sample, choosing the correct assay for screening, as well as other tedious steps that lengthen the process. These assays, however, could be valuable in detecting the homozygous deletion of exon 7 of the SMN1 gene, which is culpable in over 95% of patients with SMA.

To address these obstacles, the researchers developed a simplified NLM for detecting homozygous deletions of exon 7 of the SMN1 gene. Their test foregoes nucleic acid extraction and only requires two steps: 1) a DBS punch is taken and sent to a real-time test plate, and 2) the DBS mix is added into the well of polymerase chain reaction (PCR) assay where the screening can be directly conducted. For the purposes of their study, the authors set out to test the efficacy of their NLM for genetic screening and detecting SMN1 exon 7 homozygous deletions in patient DBS samples.

The NLM performance was evaluated on 580 DBS newborn samples, as well as 50 additional air dried whole blood DBS samples and 20 samples with known homozygous deletion of the SMN1 gene from a previous studies. The additional samples had been assessed by the Multiplex Ligation-dependent Probe Amplification (MLPA) assay; however, the researchers carrying out the wet lab portion were unaware of the MLPA results.

Researchers found each of the 580 newborn DBS samples to be wild type. In the additional samples, the NLM performed at a 100% success rate for detecting the homozygous exon 7 deletion of the SMN1 gene. Smaller punch sizes of 1.2 mm for the DBS samples yielded better results compared to punch sizes of 3.2 mm due to amplification errors. The PCR was repeated three times and similar results appeared from the 1.2 mm samples. Notably, these real-time tests were able to be conducted within 75 minutes.

The authors noted multiple benefits of the novel NLM. The 2-step process eliminated extra work associated with nucleic acid extraction from DBS. Utilizing this NLM saves times and can reduce lab errors, costs, amongst other tedious issues related to tracking and recording samples. Furthermore, the NLM does not rely on any software to operate correctly, can be used anywhere with real time PCR equipment, and does not require the harsh chemicals associated with other gene screening procedures, which provides an environmental benefit as well. Should this NLM become a standard procedure, the authors emphasize the health and economic benefits it could provide.


Kubar A, Temel SH, Beken S, et al. A direct test in spinal muscular atrophy screening for DBS. Mol Genet Genomic Med. 2023 Aug 23:e2270. doi: 10.1002/mgg3.2270.

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