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中华肾病研究电子杂志 ›› 2026, Vol. 15 ›› Issue (01) : 8 -14. doi: 10.3877/cma.j.issn.2095-3216.2026.01.002

述评

儿童遗传性肾脏病再认识
王辉1,2,(), 孙咏琪1   
  1. 1100045 北京,国家儿童医学中心,儿科重大疾病研究教育部重点实验室,首都医科大学附属北京儿童医院肾内科
    2071000 保定,国家儿童区域医疗中心、首都医科大学附属北京儿童医院保定医院肾脏内科、儿童肾脏病基础与临床重点实验室
  • 收稿日期:2025-11-26 出版日期:2026-02-28
  • 通信作者: 王辉
  • 基金资助:
    京津冀自然科学基金合作专项(25JJJJC0031)

New insights into pediatric genetic kidney disease

Hui Wang1,2,(), Yongqi Sun1   

  1. 1Department of Nephrology, Beijing Children′s Hospital Affiliated to Capital Medical University, MOE Key Laboratory of Major Diseases in Children, National Center for Children′s Health, Beijing 100045
    2Department of Nephrology, Key Laboratory of Basic and Clinical Pediatric Nephrology, Baoding Hospital of Beijing Children′s Hospital Affiliated to Capital Medical University, National Regional Center for Children′s Health, Baoding 071000, Hebei Province; China
  • Received:2025-11-26 Published:2026-02-28
  • Corresponding author: Hui Wang
引用本文:

王辉, 孙咏琪. 儿童遗传性肾脏病再认识[J/OL]. 中华肾病研究电子杂志, 2026, 15(01): 8-14.

Hui Wang, Yongqi Sun. New insights into pediatric genetic kidney disease[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2026, 15(01): 8-14.

近二十年来,随着基因检测技术的广泛应用,尤其是下一代测序技术的临床落地,儿童遗传性肾脏病的认知体系发生了深刻变革。该技术显著提高了成人及儿童遗传性肾脏病的诊断阳性率,加速了致病基因的发现与鉴定进程,同时不断拓展和丰富了经典肾脏病的基因型-表型关联谱。该技术进步推动了遗传性肾脏病分类体系的更新与重构,促使临床诊疗模式由传统的表型导向逐步转向以基因变异、病理生理机制及分子病因为核心的精准医学模式。本文基于对遗传性肾脏病发病机制及临床异质性的新认识,系统梳理并分析几种典型儿童遗传性肾脏病的基因型-表型谱演变特征,并结合现有证据提出基因检测在儿科肾脏病临床实践中的适用指征与建议,以期为遗传性肾脏病的精准诊治提供参考。

Over the past two decades, the widespread application of genetic testing technologies, particularly the clinical implementation of next-generation sequencing, has profoundly reshaped the understanding of genetic kidney diseases in children. This technological advancement has significantly improved the diagnostic yield for genetic kidney diseases in both adults and children, accelerating the discovery and identification of pathogenic genes, while continuously expanding and refining the genotype-phenotype correlations of classical renal disorders. These advances have driven the updating and reclassification of genetic kidney diseases, shifting the clinical management paradigm from a traditional phenotype-oriented approach to a precision medicine model centered on genetic variants, pathophysiological mechanisms, and molecular etiologies. Based on the renewed understanding of the pathogenesis and clinical heterogeneity of genetic kidney diseases, this article systematically reviews and analyzes the evolving genotype-phenotype spectra of several typical pediatric genetic kidney diseases. Furthermore, it proposes recommendations regarding the indications for genetic testing in clinical practice of pediatric nephrology, aiming to provide a reference for the precise diagnosis and treatment of these disorders.

图1 遗传变异与肾脏疾病[11]注:横坐标表示等位基因变异频率(代表人群频率由罕见到常见),纵坐标表示变异基因致病效应的大小(代表外显率由低到高),彩色圆圈代表基因,短线连接表示基因变异导致的疾病;根据人群频率和外显率可将肾脏病分为孟德尔肾脏病和多基因肾脏病2类,孟德尔肾脏病的相关变异罕见且外显率更高、单个变异即可致病,而多基因肾脏病相关变异常见但外显率低、需多个变异组合或与环境因素协同方能致病。
表1 基因检测的临床应用
临床应用 解释和举例说明
缩短诊断时间 对于提示可能存在遗传性肾脏病的患者,早期进行基因检测有助于明确诊断,缩短诊断花费时间,减少患者就医负担,例如SRNS等。
靶向监测并治疗肾外异常 HNF1B变异可导致一系列肾外表现,如糖尿病、肝功能损伤、生殖系统畸形等,与CAKUT相关的基因EYA1SALL1PAX2变异可能表现为听力异常,明确遗传学诊断可早期发现这些症状隐匿的疾病,尽早治疗。
指导临床治疗 SRNS患者中约30%存在单基因变异,早期进行基因检测明确遗传学诊断有助于制定正确的治疗方案,例如CoQ10合成相关基因缺陷导致的肾病综合征,尽早补充大剂量CoQ10可明显改善预后。
避免过度检查和治疗 对于病因不明CKD、SRNS患者优先进行基因检测明确诊断,如发现存在相关致病变异如NPHS1NPHS2NPHP1等,可避免进行肾活检;HNF1B变异患者可能存在肝功能异常,此为HNF1B变异相关表型的一部分,应避免如肝活检等不必要的侵入性检查。
评估疾病预后 对于某些基因,变异类型能够提供疾病进展和预后的信息,例如,Alport综合征或常染色体显性多囊肾病中,无义变异通常较错义变异患者肾脏预后更差;17q12微片段缺失较HNF1B基因点突变患者肾脏预后更好。
家系成员早期筛查,提供遗传咨询 部分遗传性肾脏病患者在疾病早期阶段可能无症状,如PAX2突变患者,通过基因检测明确家庭中某一成员的遗传学诊断后,可提醒其他家族成员尽早完善相关检查,早期发现病变并进行干预,同时指导计划生育和遗传咨询。
表2 基因检测的指征
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