NGS-based spinal muscular atrophy carrier screening of 10,585 diverse couples in China: a pan-ethnic study


In this study, we performed a spinal muscular atrophy carrier screening investigation with NGS-based method. First, the validation for NGS-based method was implemented in 2255 samples using real-time PCR. The concordance between the NGS-based method and real-time PCR for the detection of SMA carrier and patient were up to 100%. Then, we applied this NGS-based method in 10,585 self-reported normal couples (34 Chinese ethnic groups from 5 provinces in South China) for SMA carrier screening. The overall carrier frequency was 1 in 73.8 (1.4%). It varied substantially between ethnic groups, highest in Dai ethnicity (4.3%), and no significant difference was found between five provinces. One couple was detected as carriers with an elevated risk of having an SMA affected baby. The distribution of SMN1:SMN2 genotype was also revealed in this study. Among the individuals with normal phenotype, the exon 7 copy-number ratio of SMN1 to SMN2 proved the gene conversion between them. With NGS-based method, we investigated SMA carrier status in Chinese population for the first time, and our results demonstrated that it is a promising alternative for SMA carrier screening and could provide data support and reference for future clinical application.

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Fig. 1: Results of two batches of samples collected for validation and screening.

Data availability

The information of the variant detected in this study can be found at the ClinVar database ( with accession number SCV001334438. The identifiable information of the subjects used in this study is kept in our clinical laboratory to protect subjects’ privacy, while their nonidentifiable genomic sequencing data have been deposited in the CNSA ( of CNGBdb with accession code CNP0000801.


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We thank all the blood donors for their invaluable contribution to this study.


The study was supported by Special Foundation for High-level Talents of Guangdong (2016TX03R171).

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Correspondence to Jun Sun or Zhiyu Peng.

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Zhao, S., Wang, W., Wang, Y. et al. NGS-based spinal muscular atrophy carrier screening of 10,585 diverse couples in China: a pan-ethnic study. Eur J Hum Genet (2020).

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