Combining Panel-Based Next-Generation Sequencing and Exome Sequencing for Genetic Liver Diseases

Chi Bo Chen, Jacob Shujui Hsu, Pei Lung Chen, Jia Feng Wu, Huei Ying Li, Bang Yu Liou, Mei Hwei Chang, Yen Hsuan Ni, Wuh Liang Hwu, Yin Hsiu Chien, Yen-Yin Chou, Yao Jong Yang, Ni Chung Lee, Huey Ling Chen

研究成果: Article同行評審


Objectives: To determine how advanced genetic analysis methods may help in clinical diagnosis. Study design: We report a combined genetic diagnosis approach for patients with clinical suspicion of genetic liver diseases in a tertiary referral center, using tools either tier 1: Sanger sequencing on SLC2SA13, ATP8B1, ABCB11, ABCB4, and JAG1 genes, tier 2: panel-based next generation sequencing (NGS), or tier 3: whole-exome sequencing (WES) analysis. Results: In a total of 374 patients undergoing genetic analysis, 175 patients received tier 1 Sanger sequencing based on phenotypic suspicion, and pathogenic variants were identified in 38 patients (21.7%). Tier 2 included 216 patients (39 of tier 1-negative patients) who received panel-based NGS, and pathogenic variants were identified in 60 (27.8%). In tier 3, 41 patients received WES analysis, and 20 (48.8%) obtained genetic diagnosis. Pathogenic variants were detected in 6 of 19 (31.6%) who tested negative in tier 2, and a greater detection rate in 14 of 22 (63.6%) patients with deteriorating/multiorgan disease receiving one-step WES (P = .041). The overall disease spectrum is comprised of 35 genetic defects; 90% of genes belong to the functional categories of small molecule metabolism, ciliopathy, bile duct development, and membrane transport. Only 13 (37%) genetic diseases were detected in more than 2 families. A hypothetical approach using a small panel-based NGS can serve as the first tier with diagnostic yield of 27.8% (98/352). Conclusions: NGS based genetic test using a combined panel-WES approach is efficient for the diagnosis of the highly diverse genetic liver diseases.

期刊Journal of Pediatrics
出版狀態Published - 2023 7月

All Science Journal Classification (ASJC) codes

  • 兒科、圍產兒和兒童健康


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