肾脏 IV 型胶原疾病的遗传基础。
Genetic Basis of Type IV Collagen Disorders of the Kidney.
机构信息
Department of Nephrology, Royal Children's Hospital, Melbourne, Victoria, Australia.
Department of Kidney Regeneration, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
出版信息
Clin J Am Soc Nephrol. 2021 Jul;16(7):1101-1109. doi: 10.2215/CJN.19171220. Epub 2021 Apr 13.
The glomerular basement membrane is a vital component of the filtration barrier of the kidney and is primarily composed of a highly structured matrix of type IV collagen. Specific isoforms of type IV collagen, the 3(IV), 4(IV), and 5(IV) isoforms, assemble into trimers that are required for normal glomerular basement membrane function. Disruption or alteration in these isoforms leads to breakdown of the glomerular basement membrane structure and function and can lead to progressive CKD known as Alport syndrome. However, there is wide variability in phenotype among patients with mutations affecting type IV collagen that depends on a complex interplay of sex, genotype, and X-chromosome inactivation. This article reviews the genetic basis of collagen disorders of the kidney as well as potential treatments for these conditions, including direct alteration of the DNA, RNA therapies, and manipulation of collagen proteins.
肾小球基底膜是肾脏滤过屏障的重要组成部分，主要由高度结构化的 IV 型胶原基质组成。IV 型胶原的特定同工型，即 3(IV)、4(IV)和 5(IV)同工型，组装成三聚体，这是正常肾小球基底膜功能所必需的。这些同工型的破坏或改变会导致肾小球基底膜结构和功能的破坏，并可能导致称为 Alport 综合征的进行性 CKD。然而，受影响的 IV 型胶原突变的患者表型存在广泛的变异性，这取决于性别、基因型和 X 染色体失活的复杂相互作用。本文综述了肾脏胶原疾病的遗传基础以及这些疾病的潜在治疗方法，包括直接改变 DNA、RNA 疗法和胶原蛋白的操作。
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