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<p>Genetic kidney disease (GKD) is a major cause of pediatric chronic kidney disease. Many patients remain genetically unresolved by exome sequencing (ES) and copy number variation (CNV) analysis. Genome sequencing (GS) enables a comprehensive detection of genetic variations. This study evaluates a GS-based sequential strategy to determine the diagnostic yield in pediatric GKD. We recruited families with GKD from a national cohort of 23 centers from 2020 to 2024 through Chinese Children Genetic Kidney Disease Database. This sequential sequencing strategy involved initial trio-ES and Trio-CNV-seq, followed by GS in undiagnosed cases, splicing essays analysis was performed for intronic variants. A total of 735 families were enrolled. Trio-ES and Trio-CNV-seq achieved a diagnostic yield of 39.4% (35.5% from ES and 4.0% from CNV-seq). Subsequent GS identified pathogenic variants in 23 of 445 previously undiagnosed cases (5.2%), including small structural variants (5 cases), intronic variants affecting splicing function (9 cases), and variants in mitochondrion DNA (9 cases). GS showed 14% and 8.8% increase in diagnostic yield in renal tubular disease and CKD of unexplained cause. Syndromic cases exhibited a higher diagnostic yield (10.9%) than isolated cases (4.6%). These findings indicate GS-based sequential strategy improves the diagnostic yield of GKD.</p>

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Genome sequencing based sequential diagnostic strategy improve diagnosed yield of pediatric genetic kidney disease: a national multicenter study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月31日

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  • Chunyan Wang,
  • Xiaoshan Tang,
  • Xiuli Wang,
  • Shuzhen Sun,
  • Yuhong Li,
  • Yijin Song,
  • Yue Du,
  • Qingshan Ma,
  • Kaishu Zhao,
  • Dexuan Wang,
  • Qifan Zhu,
  • Xiaoshan Shao,
  • Xiaowen Wang,
  • Lin Huang,
  • Haitao Bai,
  • Yang Yang,
  • Ying Bao,
  • Pei Qian,
  • Shipin Feng,
  • Min Xie,
  • Xinli Han,
  • Rufeng Dai,
  • JiaoJiao Liu,
  • Zhiqing Zhang,
  • Qianfan Miao,
  • Zhiquan Xu,
  • Li Miao,
  • Hui Zhang,
  • Qing Sun,
  • Dandan Xin,
  • Yanyan Guo,
  • Peng Li,
  • Qiang Ma,
  • Mei Han,
  • Xiaojuan Shi,
  • Yan Zhang,
  • Junfeng Liu,
  • Xiaoqing Yang,
  • Wenli Xu,
  • Yuanhan Qin,
  • Fengying Lei,
  • Xiaoyun Jiang,
  • Liping Rong,
  • Xiqiang Dang,
  • Yongzhen Li,
  • Hongbin Zhu,
  • Ke Wu,
  • Jianxin Wang,
  • Ye Zhang,
  • Taisong Li,
  • Yihui Zhai,
  • Xiaoyan Fang,
  • Jing Chen,
  • Aihua Zhang,
  • Duan Ma,
  • Qian Shen,
  • Hong Xu

摘要

Genetic kidney disease (GKD) is a major cause of pediatric chronic kidney disease. Many patients remain genetically unresolved by exome sequencing (ES) and copy number variation (CNV) analysis. Genome sequencing (GS) enables a comprehensive detection of genetic variations. This study evaluates a GS-based sequential strategy to determine the diagnostic yield in pediatric GKD. We recruited families with GKD from a national cohort of 23 centers from 2020 to 2024 through Chinese Children Genetic Kidney Disease Database. This sequential sequencing strategy involved initial trio-ES and Trio-CNV-seq, followed by GS in undiagnosed cases, splicing essays analysis was performed for intronic variants. A total of 735 families were enrolled. Trio-ES and Trio-CNV-seq achieved a diagnostic yield of 39.4% (35.5% from ES and 4.0% from CNV-seq). Subsequent GS identified pathogenic variants in 23 of 445 previously undiagnosed cases (5.2%), including small structural variants (5 cases), intronic variants affecting splicing function (9 cases), and variants in mitochondrion DNA (9 cases). GS showed 14% and 8.8% increase in diagnostic yield in renal tubular disease and CKD of unexplained cause. Syndromic cases exhibited a higher diagnostic yield (10.9%) than isolated cases (4.6%). These findings indicate GS-based sequential strategy improves the diagnostic yield of GKD.