Targeted exome sequencing strategy (NeoEXOME) for Chinese newborns using a pilot study with 3423 neonates

作者全名："Cao, Ziyang; He, Xiaoyan; Wang, Dongjuan; Gu, Maosheng; Suo, Feng; Qiang, Rong; Zhang, Ruixue; Song, Chengrong; Wang, Xiaohua; Zhu, Bo; Cao, Donghua; Yu, Haihua; Qu, Yiping; Shen, Guosong; Wu, Jian; Wang, Pengpeng; Wang, Jinxia; Zhang, Hongyang; Yan, Zijun; Yu, Guangjun; Zou, Lin"

作者地址："[Cao, Ziyang; Wang, Jinxia; Zhang, Hongyang; Yan, Zijun; Yu, Guangjun; Zou, Lin] Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Med Sch, Clin Res Unit, Shanghai, Peoples R China; [Cao, Ziyang; Wang, Jinxia; Zhang, Hongyang; Yan, Zijun; Yu, Guangjun; Zou, Lin] Shanghai Jiao Tong Univ, Sch Med, Inst Pediat Infect Immun & Crit Care Med, Shanghai, Peoples R China; [He, Xiaoyan; Wang, Dongjuan; Zou, Lin] Chongqing Med Univ, Childrens Hosp, Ctr Clin Mol Lab Med, Chongqing, Peoples R China; [Gu, Maosheng; Suo, Feng] Xuzhou Maternal & Child Hlth Care Hosp, Ctr Med Genet, Xuzhou, Peoples R China; [Qiang, Rong; Zhang, Ruixue; Song, Chengrong] Northwest Women & Childrens Hosp, Ctr Med Genet, Xian, Peoples R China; [Wang, Xiaohua; Zhu, Bo] Inner Mongolia Maternal & Child Hlth Care Hosp, Ctr Med Genet, Hohhot, Peoples R China; [Cao, Donghua; Yu, Haihua] Dalian Municipal Women & Childrens Med Ctr Grp, Med Genet Lab, Dalian, Peoples R China; [Cao, Donghua] Shenyang Jinghua Hosp Co Ltd, Genet Lab, Shenyang, Peoples R China; [Qu, Yiping] Zhejiang Univ, Childrens Hosp, Sch Med, Newborn Screening Ctr, Hangzhou, Peoples R China; [Shen, Guosong] Huzhou Maternal & Child Hlth Care Hosp, Med Lab Ctr, Huzhou, Peoples R China; [Wu, Jian; Wang, Pengpeng] MyGenostics Inc, Res & Dev Dept, Beijing, Peoples R China"

通信作者："Yu, GJ; Zou, L (通讯作者)，Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Med Sch, Clin Res Unit, Shanghai, Peoples R China.; Yu, GJ; Zou, L (通讯作者)，Shanghai Jiao Tong Univ, Sch Med, Inst Pediat Infect Immun & Crit Care Med, Shanghai, Peoples R China.; Zou, L (通讯作者)，Chongqing Med Univ, Childrens Hosp, Ctr Clin Mol Lab Med, Chongqing, Peoples R China."

来源：MOLECULAR GENETICS & GENOMIC MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001144621600001

JCR分区：Q3

影响因子：2

年份：2024

卷号：12

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：monogenic inherited diseases; NeoEXOME panel performance; newborn screening; pilot study; targeted sequencing

摘要："Background: Newborn screening (NBS) aims to detect congenital anomalies, and next-generation sequencing (NGS) has shown promise in this aspect. However, the NBS strategy for monogenic inherited diseases in China remains insufficient.Methods: We developed a NeoEXOME panel comprising 601 genes that are relevant to the Chinese population found through extensive research on available databases. An interpretation system to grade the results into positive (high-risk, moderate-risk, and low-risk genotypes), negative, and carrier according to the American College of Medical Genetics (ACMG) guidelines was also developed. We validated the panel to evaluate its efficacy by using data from the ""1000 Genomes Project"" and conducted a pilot multicenter study involving 3423 neonates.Results: The NGS positive rate in the 1000 Genomes Project was 7.6% (23/301), whereas the rate was 12.0% in the multicenter study, including 3249 recruited neonates. Notably, in 200 neonates, positive per conventional NBS, 58.5% (69/118) showed results consistent with NGS. In the remaining 3049 neonates showing negative results in conventional NBS, 271 (8.9%) were positive per NGS, and nine of them were clinically diagnosed with diseases in the follow-up.Conclusion: We successfully designed a NeoEXOME panel for targeted sequencing of monogenic inherited diseases in NBS. The panel demonstrated high performance in the Chinese population, particularly for the early detection of diseases with no biochemical markers."

基金机构：Chongqing Science and Technology Bureau

基金资助正文：We thank all the participants and their guardians in the research.