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

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

doi:10.1002/mgg3.2357

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

Mol Genet Genomic Med. 2024 Jan;12(1):e2357. doi: 10.1002/mgg3.2357.

Authors

Ziyang Cao^{1

2}, Xiaoyan He³, Dongjuan Wang³, Maosheng Gu⁴, Feng Suo⁴, Rong Qiang⁵, Ruixue Zhang⁵, Chengrong Song⁵, Xiaohua Wang⁶, Bo Zhu⁶, Donghua Cao^{7

8}, Haihua Yu⁷, Yiping Qu⁹, Guosong Shen¹⁰, Jian Wu¹¹, Pengpeng Wang¹¹, Jinxia Wang^{1

2}, Hongyang Zhang^{1

2}, Zijun Yan^{1

2}, Guangjun Yu^{1

2}, Lin Zou^{1

2

3}

Affiliations

¹ Clinical Research Unit, Shanghai Children's Hospital, Shanghai Jiao Tong University Medical School, Shanghai, China.
² Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Center for Clinical Molecular Laboratory Medicine of Children's Hospital of Chongqing Medical University, Chongqing, China.
⁴ Center of Medical Genetics, Xuzhou Maternal and Child Health Care Hospital, Xuzhou, China.
⁵ Center of Medical Genetics, Northwest Women and Children's Hospital, Xi'an, China.
⁶ Center of Medical Genetics, Inner Mongolia Maternal and Child Health Care Hospital, Hohhot, China.
⁷ Medical Genetic Laboratory, Dalian Municipal Women and Children's Medical Center (Group), Dalian, China.
⁸ Genetic Laboratory, Shenyang Jinghua Hospital Co., Ltd, Shenyang, China.
⁹ Newborn Screening Center of Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.
¹⁰ Medical Laboratory Center of Huzhou Maternal and Child Health Care Hospital, Huzhou, China.
¹¹ Research and Development Department, MyGenostics Inc., Beijing, China.

Abstract

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.

Keywords: NeoEXOME panel performance; monogenic inherited diseases; newborn screening; pilot study; targeted sequencing.

Publication types

Multicenter Study

MeSH terms

Exome Sequencing
Genotype
High-Throughput Nucleotide Sequencing* / methods
Humans
Infant, Newborn
Neonatal Screening* / methods
Pilot Projects

Abstract

Publication types

MeSH terms

Grants and funding