芯片捕获二代测序技术在新生儿疾病筛查中的应用  

Clinical application of newborn screening based on chip capture second-generation sequencing technology

作　　者：王欣[1] 孙云[1] 王彦云[1] 洪冬洋 管贤伟 蒋涛[1] 许争峰[1] WANG Xin;SUN Yun;Wang Yanyun;HONG Dongyang;Guan Xianwei;JIANG Tao;Xu Zhengfeng(Women′s Hospital of Nanjing Medical University&Nanjing Maternity and Child Health Care Hospital Genetic Medicine Center,Nanjing 210004,Jiangsu,China)

机构地区：[1]南京医科大学附属妇产医院&南京市妇幼保健院遗传医学中心,南京210004

出　　处：《临床检验杂志》2022年第3期173-178,共6页Chinese Journal of Clinical Laboratory Science

基　　金：国家重点研发计划(2018YFC1002400);南京医科大学科技发展基金(NMUB2019215,NMUB2020122)。

摘　　要：目的探讨芯片捕获二代测序技术在新生儿疾病筛查中的临床应用价值。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报道致病位点进行检测,检出位点采用Sanger测序验证。结果150例样本中有4例为可疑阳性患者(阳性率为2.67%),88例为致病基因携带者(携带率为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40.7%,最多可见携带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,其次为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,可有效降低筛查假阳性率,提高阳性预测值,具有重要的临床价值。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 newborns and the targeted capture-based NGS method,the reported pathogenic sites of the pathogenic genes that cause the 169 common inherited diseases of the newborns were detected,and the pathogenic 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 deafness genes GJB2 and SLC26A4,followed by PAH,SLC22A5,DUOX2,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 effectively reduce the traditional false-positive rate and improve the positive predictive value which play an important role in clinic.

关 键 词：基因筛查 芯片捕获二代测序 遗传代谢病 新生儿筛查 

分 类 号：R446[医药卫生—诊断学] R722.11[医药卫生—临床医学]