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

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

doi:10.1016/j.jgg.2021.08.008

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

J Genet Genomics. 2022 Jan;49(1):13-19. doi: 10.1016/j.jgg.2021.08.008. Epub 2021 Aug 30.

Authors

Chanjuan Hao¹, Ruolan Guo², Xuyun Hu², Zhan Qi², Qi Guo², Xuanshi Liu², Yuanhu Liu², Yanhua Sun³, Xiaofen Zhang³, Feng Jin³, Xiujie Wu³, Ren Cai⁴, Dingyuan Zeng⁴, Xijiang Hu⁵, Xiaohua Wang⁶, Xiaoping Ji⁶, Wenjie Li⁷, Quansheng Xing⁷, Lanfang Mu⁸, Xiulian Jiang⁸, Xue Yang⁹, Weimin Yang⁹, Yan Zhang¹⁰, Qianli Yin¹⁰, Xin Ni¹¹, Wei Li¹²

Affiliations

¹ Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing 100045, China; MOE Key Laboratory of Major Diseases in Children, Beijing 100045, China; Rare Disease Center, National Center for Children's Health, Beijing 100045, China; Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. Electronic address: hchjhchj@163.com.
² Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing 100045, China; MOE Key Laboratory of Major Diseases in Children, Beijing 100045, China; Rare Disease Center, National Center for Children's Health, Beijing 100045, China; Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
³ Shunyi Women and Children's Healthcare Hospital of Beijing Children's Hospital, Beijing 101300, China.
⁴ Liuzhou Maternal and Child Healthcare Hospital, Liuzhou, Guangxi 545001, China.
⁵ Wuhan Maternal and Child Healthcare Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430016, China.
⁶ Inner Mongolia Maternity and Child Healthcare Hospital, Hohhot, Inner Mongolia Autonomous Region 010020, China.
⁷ Qingdao Women and Children's Hospital, Qingdao, Shandong 266012, China.
⁸ Qinghai Maternal and Child Health Hospital, Xining, Qinghai 810007, China.
⁹ Guiyang Maternity and Child Healthcare Hospital, Guiyang, Guizhou 550003, China.
¹⁰ Urumqi First People's Hospital, Urumqi, Xinjiang 830011, China.
¹¹ Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing 100045, China; MOE Key Laboratory of Major Diseases in Children, Beijing 100045, China; Rare Disease Center, National Center for Children's Health, Beijing 100045, China; Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. Electronic address: nixin@bch.com.cn.
¹² Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing 100045, China; MOE Key Laboratory of Major Diseases in Children, Beijing 100045, China; Rare Disease Center, National Center for Children's Health, Beijing 100045, China; Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. Electronic address: liwei@bch.com.cn.

PMID: 34474183
DOI: 10.1016/j.jgg.2021.08.008

Abstract

Different newborn screening (NBS) programs have been practiced in many countries since the 1960s. 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.

Keywords: Clinical practice; Monogenic disorders; Newborn screening; Next-generation sequencing; Targeted sequencing.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Child
China / epidemiology
Female
High-Throughput Nucleotide Sequencing* / methods
Humans
Infant
Infant, Newborn
Male
Neonatal Screening* / methods
Retrospective Studies