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

作者：Zhao, Sumin; Wang, Wanyang; Wang, Yaoshen; Han, Rui; Fan, Chunna; Ni, Peixiang; Guo, Fengyu; Zeng, Fanwei; Yang, Qiaona; Yang, Yun; Sun, Yan; Zhang, Xinhua; Chen, Yan; Zhu, Baosheng; Cai, Wangwei; Chen, Shaoke; Cai, Ren; Guo, Xiaoling; Zhang, Chonglin; Zhou, Yuqiu; Huang, Shuodan; Liu, Yanhui; Chen, Biyan; Yan, Shanhuo; Chen, Yajun; Ding, Hongmei; Shang, Xuan; Xu, Xiangmin; Sun, Jun^*; Peng, Zhiyu^*

来源：European Journal of Human Genetics, 2021, 29(1): 194-204.

DOI：10.1038/s41431-020-00714-8

• COPY-NUMBER
• NEXT-GENERATION
• SMN1
• SMA
• IDENTIFICATION
• GENES
• SEQUENCE
• PROTEIN
• REGION
• ALLELE

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.

• 单位
  海南医学院; 深圳华大基因研究院; 南方医科大学; 河北医科大学; 1