Hui Xiao1, Jian-Tao Zhang1, Xin-Ran Dong2, Yu-Lan Lu2, Bing-Bing Wu2, Hui-Jun Wang2, Zheng-Yan Zhao3, Lin Yang4,5, Wen-Hao Zhou6,7. 1. Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China. 2. Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. 3. Department of Child Health Care, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China. 4. Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. linyang09@fudan.edu.cn. 5. Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China. linyang09@fudan.edu.cn. 6. Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China. zhouwenhao@fudan.edu.cn. 7. Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China. zhouwenhao@fudan.edu.cn.
Abstract
BACKGROUND: During next generation sequencing (NGS) data interpretation in critically ill newborns, there is a potential for recognizing and reporting secondary findings (SFs). Early awareness of SFs may provide clues for disease prevention. In this study, we assessed the frequency of SFs in the China Neonatal Genomes Project (CNGP) participants. METHODS: A total of 2020 clinical exome sequencing (CES) datasets were screened for variants from a list of 59 genes recommended by the American College of Medical Genetics and Genomics (ACMG) for secondary findings reporting v2.0 (ACMG SF v2.0). Identified variants were classified according to the evidence-based guidelines reached by a joint consensus of the ACMG and the Association for Molecular Pathology (AMP). RESULTS: Among the 2020 CES datasets, we identified 23 ACMG-reportable genes in 61 individuals, resulting in an overall frequency of SFs at 3.02%. A total of 53 unique variants were identified, including 35 pathogenic and 18 likely pathogenic variants. The common disease categories of SFs associated were cardiovascular and cancer disease. The SF results affected the medical management and follow-up strategy in 49 (80.3%) patients. CONCLUSIONS: We presented the frequency of SFs and their impact on clinical management strategies in CNGP participants. Our study demonstrated that SFs have important practical value in disease prevention and intervention at an early stage.
BACKGROUND: During next generation sequencing (NGS) data interpretation in critically ill newborns, there is a potential for recognizing and reporting secondary findings (SFs). Early awareness of SFs may provide clues for disease prevention. In this study, we assessed the frequency of SFs in the China Neonatal Genomes Project (CNGP) participants. METHODS: A total of 2020 clinical exome sequencing (CES) datasets were screened for variants from a list of 59 genes recommended by the American College of Medical Genetics and Genomics (ACMG) for secondary findings reporting v2.0 (ACMG SF v2.0). Identified variants were classified according to the evidence-based guidelines reached by a joint consensus of the ACMG and the Association for Molecular Pathology (AMP). RESULTS: Among the 2020 CES datasets, we identified 23 ACMG-reportable genes in 61 individuals, resulting in an overall frequency of SFs at 3.02%. A total of 53 unique variants were identified, including 35 pathogenic and 18 likely pathogenic variants. The common disease categories of SFs associated were cardiovascular and cancer disease. The SF results affected the medical management and follow-up strategy in 49 (80.3%) patients. CONCLUSIONS: We presented the frequency of SFs and their impact on clinical management strategies in CNGP participants. Our study demonstrated that SFs have important practical value in disease prevention and intervention at an early stage.
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