Cosgrove Dominic, Madison Jacob
Boys Town National Research Hospital, Omaha, NE, United States.
Front Med (Lausanne). 2022 Feb 9;9:846152. doi: 10.3389/fmed.2022.846152. eCollection 2022.
Alport syndrome results from a myriad of variants in the COL4A3, COL4A4, or COL4A5 genes that encode type IV (basement membrane) collagens. Unlike type IV collagen α1(IV)α2(IV) heterotrimers, which are ubiquitous in basement membranes, α3/α4/α5 have a limited tissue distribution. The absence of these basement membrane networks causes pathologies in some, but not all these tissues. Primarily the kidney glomerulus, the stria vascularis of the inner ear, the lens, and the retina as well as a rare link with aortic aneurisms. Defects in the glomerular basement membranes results in delayed onset and progressive focal segmental glomerulosclerosis ultimately requiring the patient to undergo dialysis and if accessible, kidney transplant. The lifespan of patients with Alport syndrome is ultimately significantly shortened. This review addresses the consequences of the altered glomerular basement membrane composition in Alport syndrome with specific emphasis on the mechanisms underlying initiation and progression of glomerular pathology.
奥尔波特综合征由编码IV型（基底膜）胶原蛋白的COL4A3、COL4A4或COL4A5基因中的多种变异引起。与在基底膜中普遍存在的IV型胶原蛋白α1(IV)α2(IV)异源三聚体不同，α3/α4/α5的组织分布有限。这些基底膜网络的缺失会在部分而非所有这些组织中引发病变。主要累及肾小球、内耳的血管纹、晶状体、视网膜，以及与主动脉瘤的罕见关联。肾小球基底膜的缺陷会导致发病延迟和进行性局灶节段性肾小球硬化，最终患者需要接受透析治疗，若有合适的肾脏，还需进行肾移植。奥尔波特综合征患者的寿命最终会显著缩短。本综述探讨了奥尔波特综合征中肾小球基底膜成分改变的后果，特别强调了肾小球病变起始和进展的潜在机制。
