国家重点研发计划 (No. 2018YFC1002400)；南京医科大学科技发展基金项目（NMUB2020122，NMUB2019215）
目的 探讨基于芯片捕获二代测序技术的新生儿疾病筛查临床应用价值。方法 收集新生儿遗传代谢病筛查干血滤纸片回顾性样本,采用芯片捕获二代测序技术,对169种常见疾病致病基因的已知位点进行检测,检出位点通过Sanger测序验证。结果 150例样本中4例为可疑阳性患者(阳性率2.67%)。88例为致病基因携带(携带率58.67%)。58例未检测到致病基因变异。其中,携带1个致病基因变异的样本高达40%,最多可见有携带4个不同的致病基因变异。携带频率最高的致病基因为GJB2和SLC26A4,其次是PAH、SLC22A5、DUOX2、SLC12A3、USH2A及ACADS。结论 基于芯片捕获二代测序技术的新生儿疾病筛查扩大了筛查病种。与传统生化筛查结果进行结合和分析,可有效降低假阳性率,避免漏筛,有着重要的临床价值。
Abstract: Objective To explore the clinical value of newborn screening based on the targeted capture-based NGS. Methods Using the retrospective dry blood spot samples on the foot of the newborms and the targeted capture-based NGS method, the reported pathogenic sites of the pathogenic genes that cause the 169 conmon inherited diseases of the newborns were detected ，and the pathogenie sites were verified by sanger sequencing. Results It was found that 4 out of 150 samples were suspected positive samples, and the positive rate was 2.67%. 88 cases were pathogenic genes carriers, and the carrying rate of pathogenic genes was about 58.67%. There are no pathogenic gene variants detected in the residual 58 cases. Among them, as many as 40.7% of the samples carrying 1 pathogenic gene variant, and up to 4 different pathogenic gene variants been carried also can be seen. The most frequently carried pathogenic genes were deafiness genes GJB2 and SLC26A4, followed by PAH, SLC22A5, DU0X2, SLC12A3, USH2A and ACADS. Conclusion Newborn screening based on targeted capture-based NGS can expanded the screening of diseases. In addition, the combination and analysis with traditional biochemical screening results can efctively reduce the traditional false-positive rate and improve the positive predictive value which play an important role in clinic.