Newborn screening with targeted sequencing:a multicenter investigation and a pilot clinical study in China  

作　　者：Chanjuan Hao Ruolan Guo Xuyun Hu Zhan Qi Qi Guo Xuanshi Liu Yuanhu Liu Yanhua Sun Xiaofen Zhang Feng Jin Xiujie Wu Ren Cai Dingyuan Zeng Xijiang Hu Xiaohua Wang Xiaoping Ji Wenjie Li Quansheng Xing Lanfang Mu Xiulian Jiang Xue Yang Weimin Yang Yan Zhang Qianli Yin Xin Ni Wei Li 

机构地区：[1]Beijing Key Laboratory for Genetics of Birth Defects,Beijing Pediatric Research Institute,Beijing 100045,China [2]MOE Key Laboratory of Major Diseases in Children,Beijing 100045,China [3]Rare Disease Center,National Center for Children’s Health,Beijing 100045,China [4]Beijing Children’s Hospital,Capital Medical University,Beijing 100045,China [5]Shunyi Women and Children’s Healthcare Hospital of Beijing Children’s Hospital,Beijing 101300,China [6]Liuzhou Maternal and Child Healthcare Hospital,Liuzhou,Guangxi 545001,China [7]Wuhan Maternal and Child Healthcare Hospital,Tongji Medical College,Huazhong University of Science&Technology,Wuhan,Hubei 430016,China [8]Inner Mongolia Maternity and Child Healthcare Hospital,Hohhot,Inner Mongolia Autonomous Region 010020,China [9]Qingdao Women and Children’s Hospital,Qingdao,Shandong 266012,China [10]Qinghai Maternal and Child Health Hospital,Xining,Qinghai 810007,China [11]Guiyang Maternity and Child Healthcare Hospital,Guiyang,Guizhou 550003,China [12]Urumqi First People’s Hospital,Urumqi,Xinjiang 830011,China

出　　处：《Journal of Genetics and Genomics》2022年第1期13-19,共7页遗传学报（英文版）

基　　金：partially supported by grants from the Ministry of Science and Technology of China(2016YFC1000306);the Beijing Municipal Science and Technology Commission Foundation(Z181100001918003);the Beijing Municipal Commission of Health and Family Planning Foundation(2018-21141,2020-4-1144);Beihang University&Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan(BHME-201905)。

摘　　要：Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.

关 键 词：Newborn screening Next-generation sequencing Targeted sequencing Monogenic disorders Clinical practice 

分 类 号：R722.1[医药卫生—儿科]