Carrier Screening and Diagnosis for Spinal Muscular Atrophy Using Droplet Digital PCR Versus MLPA: Analytical Validation and Early Test Outcome.
Genet Test Mol Biomarkers
; 28(5): 207-212, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38533877
ABSTRACT
Background:
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular life-threatening disorder. Owing to high carrier frequency, population-wide SMA screening to quantify the copy number of SMN gene is recommended by American College of Medical Genetics and Genomics. An accurate, reliable, short runaround time and cost-effective method may be helpful in mass population screening for SMA.Methods:
Multiplex ligation-dependent probe amplification (MLPA) is a gold standard to estimate the copy number variation (CNV) for SMN1 and SMN2 genes. In this study, we validated droplet digital polymerase chain reaction (ddPCR) for the determination of CNV for both SMN1 and SMN2 exon 7 for a diagnostic purpose. In total, 66 clinical samples were tested using ddPCR, and results were compared with the MLPA as a reference test.Results:
For all samples, CNV for SMN1 and SMN2 exon 7 was consentaneous between ddPCR and MLPA test results (κ = 1.000, p < 0.0001). In addition, ddPCR also showed a significant acceptable degree of test repeatability, coefficient of variation < 4%.Conclusion:
ddPCR is expected to be utilitarian for CNV detection for carrier screening and diagnosis of SMA. ddPCR test results for CNV detection for SMN1/SMN2 exon 7 are concordant with the gold standard. ddPCR is a more cost-effective and time-saving diagnostic test for SMA than MLPA. Furthermore, it can be used for population-wide carrier screening for SMA.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Muscular Atrophy, Spinal
/
Exons
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Survival of Motor Neuron 1 Protein
/
Survival of Motor Neuron 2 Protein
/
DNA Copy Number Variations
/
Multiplex Polymerase Chain Reaction
/
Genetic Carrier Screening
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Genet Test Mol Biomarkers
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA
Year:
2024
Document type:
Article
Affiliation country:
India
Country of publication:
Estados Unidos