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Carrier screening for spinal muscular atrophy with a simple test based on melting analysis


Carrier screening of spinal muscular atrophy (SMA) can provide reproductive options for carriers and prevent the birth defects. Here, we developed a simple screening test based on melting analysis. The test comprises a duplex PCR with two primer pairs and three probes to simultaneous amplify SMN1, SMN2, and CFTR. By analyzing the melting profiles, we were able to determine the SMN1/SMN2 ratio and SMN1 + SMN2 copy number to subsequently determine the copy number of SMN1. Samples with one copy of SMN1 were considered as “high risk for carrier,” while samples with ≥2 copies of SMN1 were considered as “low risk for carrier.” We evaluated the clinical performance of this test using 215 clinical samples with various genotypes that had been previously confirmed by multiplex ligation-dependent probe amplification (MLPA). The test showed high sensitivity (100%) and specificity (97.1%) as well as high positive (97.3%) and negative (100%) predictive value, and was in perfect agreement with the gold standard test, MLPA (k = 0.97). Moreover, it is rapid, inexpensive, and easy to perform and automate, with high reproducibility and capacity. Therefore, we expect this test will advance carrier screening for SMA.

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We would like to thank the patients and their families for their contributions in this study. This work was supported by the Foundation for Young Scholars of Fujian Provincial Department of Health Office (project no. 2017-2-107), National Natural Science Foundation of China (project No. 81572084), and Xiamen Science and Technology Major Project (project No. 3502Z20171006).



This work was supported by the Foundation for Young Scholars of Fujian Provincial Department of Health Office (project no. 2017-2-107), National Natural Science Foundation of China (project No. 81572084), and Xiamen Science and Technology Major Project (project No. 3502Z20171006).

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Correspondence to Jun Ren or Qiwei Guo.

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Xia, Z., Zhou, Y., Fu, D. et al. Carrier screening for spinal muscular atrophy with a simple test based on melting analysis. J Hum Genet 64, 387–396 (2019).

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