Xcelom Limited (Global)
Long-read sequencing
Comprehensive Analysis of Spinal Muscular Atrophy (CASMA)
Covers the most SMA possibilities in one test
The Challenges of Spinal Muscular Atrophy Testing
Spinal Muscular Atrophy (SMA) is primarily caused by defect in the SMN1 gene. Molecular testing for SMA presents a challenge due to the high sequence homology between SMN1 and SMN2, which may compensate for the loss of SMN1 and modify the severity of the disease. Conventional assays, such as qPCR and MLPA, are targeting the c.840C site in exon 7 as a SMN1 copy marker, which does not always represent the actual functional copy on each chromosome. These routine methods cannot assess the possibility of non-exon 7 deletions, SMN1 variants, or the '2+0' status. As a result, approximately 9% of SMA carriers ([2+0], [1+1D], and [2+1D]) are missed by current routine testing.¹⁻⁴
![Conventional genetic assays fail to detect SMN1 gene defects caused by small variants and cannot identify [2+0] carriers, who](https://static.wixstatic.com/media/4cc87c_4704163c14eb4543b24945982df99bc0~mv2.png/v1/crop/x_0,y_0,w_1103,h_359/fill/w_973,h_317,al_c,q_85,usm_0.66_1.00_0.01,enc_avif,quality_auto/TGS-SMA%20technology%20transfer%20v1_2.png)
Information derived from reference 1-4
A Ultimate Thalassemia Clinical Solution
Comprehensive Analysis of Spinal Muscular Atrophy (CASMA) CASMA offers a single-assay solution capable of detecting all mutations in SMN1, while simultaneously determining both SMN1 and SMN2 copy numbers with >99% accuracy.⁵ The [2+0] family trio analysis add-on can identify [2+0] carriers without the need for a proband. This facilitates accurate carrier identification and supports clinicians in managing even the complex cases of SMA with confidence.
Comparison
Variant | qPCR | MLPA | NGS | CASMA |
|---|---|---|---|---|
SMN1/SMN2 copy number | ✔ | ✔ | ✔ | ✔ |
SMN1 variants | ✕ | ✕ | ✕ | ✔ |
[2+0] carrier | ✕ | ✕ | ✕ | ✔ |
Xcelom Limited and Berry Genomics provide a comprehensive end-to-end technology transfer solution for conducting clinical tests within your facility.
From Sample to Report:
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Laboratory setup and consultation
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End-to-end Workflow: SOPs, reagent, and training
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Analysis Software: From sample management to report generation
Platform
PacBio Vega, Sequel II, and Sequel IIe system
Sample Type
gDNA from dried blood spot, blood, and buccal swab
Test per Batch
Max. 384 Tests per SMRT Cell (Mixed Batching Supported)
Operation Time
~ 80 hours (Hand on time: ~10.5 hours)
Automation Capability
Yes
Coverage
Targets full-length of SMN1 and SMN2 gene
Resources
CASMA Brochure
References:
1. Smith M, Calabro V, Chong B, Gardiner N, Cowie S, du Sart D. Population screening and cascade testing for carriers of SMA. Eur J Hum Genet. 2007;15(7):759-766.
2.Qu YJ, Bai JL, Cao YY, et al. Mutation Spectrum of the Survival of Motor Neuron 1 andFunctional Analysis of Variants in Chinese Spinal Muscular Atrophy. J Mol Diagn. 2016;18(5):741-752.
3.Mailman MD, Hemingway T, Darsey RL, et al. Hybrids monosomal for human chromosome 5 reveal the presence of a spinal muscular atrophy (SMA) carrier with two SMN1 copies on one chromosome. Hum Genet. 2001;108(2):109-115.
4.Medical Genetics Branch of Beijing Medical Association, and Beijing Rare Disease Diagnosis and Protection Association. Expert consensus on the genetic diagnosis of spinal muscular atrophy. National Medical Journal of China. 2020, 100(40):3130-31140.
5. Bai J, Qu Y, Huang W, et al. A high-fidelity long-read sequencing-based approach enables accurate and effective genetic diagnosis of spinal muscular atrophy. Clin Chim Acta. 2024;553:117743.