COL4A3、COL4A4和COL4A5基因变异相关的肾脏疾病及其致病机制
收稿日期: 2025-09-01
录用日期: 2025-12-31
网络出版日期: 2026-03-31
基金资助
国家自然科学基金项目(82570813)
Kidney diseases related to COL4A3, COL4A4 and COL4A5 gene variations and their pathogenic mechanisms
Received date: 2025-09-01
Accepted date: 2025-12-31
Online published: 2026-03-31
胶原Ⅳ是肾小球基底膜的核心结构蛋白，由COL4A3、COL4A4和COL4A5基因编码的α链组装形成α3α4α5三聚体，对维持肾小球基底膜的结构完整性和滤过功能至关重要。这3个基因变异可导致一系列遗传性肾脏疾病，其中Alport综合征是最典型的代表，临床以血尿、进行性肾功能减退、感音神经性耳聋和眼部异常为特征，遗传模式涵盖X连锁、常染色体隐性和常染色体显性。此外，COL4A3、COL4A4和COL4A5基因变异还与薄基底膜肾病（TBMN）、家族性IgA肾病、局灶节段性肾小球硬化（FSGS）、激素抵抗性肾病综合征（SRNS）以及不明原因的终末期肾病（ESRD）等多种肾脏疾病密切相关。近年来，随着高通量测序技术的广泛应用，基因检测在疾病诊断、预后评估和精准治疗中的价值日益凸显。本文系统综述了COL4A3至COL4A5基因相关肾脏疾病的临床表现、分子遗传机制及其临床管理策略，以期为该类疾病的早期诊断和个体化治疗提供理论依据和实践指导。
李浩淼 , 张晓宇 , 韩媛 , 车若琛 , 陈秋霞 , 赵三龙 , 丁桂霞 . COL4A3、COL4A4和COL4A5基因变异相关的肾脏疾病及其致病机制[J]. 临床儿科杂志, 2026 , 44(4) : 362 -372 . DOI: 10.12372/jcp.2026.25e1075
Collagen Ⅳ is the core structural protein of the glomerular basement membrane, composed of α chains encoded by the COL4A3, COL4A4, and COL4A5 genes, which assemble into the α3α4α5 trimer. It plays a crucial role in maintaining the structural integrity and filtration function of the glomerular basement membrane. Variations in these three genes can lead to a spectrum of inherited kidney diseases, with Alport syndrome being the most representative. Clinically, Alport syndrome is characterized by hematuria, progressive renal dysfunction, sensorineural hearing loss, and ocular abnormalities, with inheritance patterns including X-linked, autosomal recessive, and autosomal dominant. Additionally, variations in the COL4A3-COL4A5 genes are closely associated with various kidney diseases, such as thin basement membrane nephropathy (TBMN), familial IgA nephropathy, focal segmental glomerulosclerosis (FSGS), steroid-resistant nephrotic syndrome (SRNS), and end-stage renal disease (ESRD) of unknown etiology. In recent years, with the widespread application of high-throughput sequencing technologies, genetic testing has increasingly demonstrated its value in disease diagnosis, prognosis assessment, and precision medicine. This article systematically reviews the clinical manifestations, molecular genetic mechanisms, and clinical management strategies of COL4A3-COL4A5-related kidney diseases, aiming to provide a theoretical foundation and practical guidance for early diagnosis and individualized treatment of these conditions.
Key words： collagen Ⅳ; Alport syndrome; genetic testing; chronic kidney disease
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