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

• 影响指数: 5.351
• 发表时间: 01 2021
• 来源期刊: Eur J Hum Genet
• DOI: 10.1038/s41431-020-00714-8
• PMID: 32884118
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 生物
• 作者列表: Zhao S,Wang W,Wang Y,Han R,Fan C,Ni P,Guo F,Zeng F,Yang Q,Yang Y,Sun Y,Zhang X,Chen Y,Zhu B,Cai W,Chen S,Cai R,Guo X,Zhang C,Zhou Y,Huang S,Liu Y,Chen B,Yan S,Chen Y,Ding H,Shang X,Xu X,Sun J,Peng Z

Mesh: China; Ethnicity / genetics; Female; Gene Conversion; Gene Frequency; Genetic Carrier Screening / statistics & numerical data; High-Throughput Nucleotide Sequencing / statistics & numerical data; Humans; Male; Muscular Atrophy, Spinal / ethnology genetics; Sequence Analysis, DNA / statistics & numerical data; Survival of Motor Neuron 1 Protein / genetics; Survival of Motor Neuron 2 Protein / genetics

Abstract

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.