Targeted exome sequencing strategy (NeoEXOME) for Chinese newborns using a pilot study with 3423 neonates
Ziyang Cao1,2, Xiaoyan He3, Dongjuan Wang3
1Clinical Research Unit, Shanghai Children's Hospital, Shanghai Jiao Tong University Medical School, Shanghai, China.
Molecular Genetics & Genomic Medicine
|January 29, 2024
Summary
A new NeoEXOME panel effectively screens for monogenic inherited diseases in Chinese newborns using next-generation sequencing (NGS). This targeted approach improves early detection, especially for conditions lacking biochemical markers.
Area of Science:
- Genetics
- Genomics
- Pediatrics
Background:
- Newborn screening (NBS) is crucial for detecting congenital anomalies.
- Current NBS strategies for monogenic inherited diseases in China are insufficient.
- Next-generation sequencing (NGS) shows potential for improving NBS.
Purpose of the Study:
- To develop and validate a targeted sequencing panel for monogenic inherited diseases in the Chinese newborn population.
- To enhance the efficacy of newborn screening through advanced genetic analysis.
Main Methods:
- Developed a NeoEXOME panel of 601 genes relevant to the Chinese population.
- Created an interpretation system based on ACMG guidelines for result grading.
- Validated the panel using the 1000 Genomes Project and a pilot multicenter study of 3423 neonates.
Main Results:
- The NGS positive rate was 7.6% in the 1000 Genomes Project and 12.0% in the multicenter study.
- Of neonates positive by conventional NBS, 58.5% were consistent with NGS results.
- Among neonates negative by conventional NBS, 8.9% were positive by NGS, with nine clinically diagnosed post-follow-up.
Conclusions:
- Successfully designed and validated the NeoEXOME panel for targeted sequencing in NBS.
- The panel demonstrated high performance in the Chinese population for detecting monogenic inherited diseases.
- This approach enables early detection of diseases, particularly those without biochemical markers.
