Shenzhen Key Laboratory of Renal, Department of Nephrology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Guangdong, China.
The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, Guangdong, China.
Biosci Rep. 2021 Jan 29;41(1). doi: 10.1042/BSR20203248.
Focal segmental glomerulosclerosis (FSGS), a type of primary glomerular disease, is the leading cause of end-stage renal disease (ESRD). Several studies have revealed that certain single-gene mutations are involved in the pathogenesis of FSGS; however, the main cause of FSGS has not been fully elucidated. Homozygous mutations in the glomerular basement membrane gene can lead to early renal failure, while heterozygous carriers develop renal failure symptoms late. Here, molecular genetic analysis of clinical information collected from clinical reports and medical records was performed. Results revealed that nephrosis 2 (NPHS2) gene polymorphism aggravated renal damage in three FSGS families with heterozygous COL4A3 mutation, leading to early renal failure in index patients. Our findings suggest that COL4A3 and NPHS2 may have a synergistic effect on renal injury caused by FSGS. Further analysis of the glomerular filtration barrier could help assess the cause of kidney damage. Moreover, a detailed analysis of the glomerular basement membrane-related genes and podocyte structural proteins may help us better understand FSGS pathogenesis and provide insights into the prognosis and treatment of hereditary glomerulonephropathy.
局灶节段性肾小球硬化症（FSGS）是一种原发性肾小球疾病，是终末期肾病（ESRD）的主要原因。几项研究表明，某些单基因突变与 FSGS 的发病机制有关；然而，FSGS 的主要原因尚未完全阐明。肾小球基底膜基因的纯合突变可导致早期肾衰竭，而杂合携带者则会出现晚期肾衰竭症状。在这里，对从临床报告和病历中收集的临床信息进行了分子遗传学分析。结果表明，在三个具有杂合 COL4A3 突变的 FSGS 家族中，肾病 2 （NPHS2）基因多态性加重了肾脏损伤，导致指数患者出现早期肾衰竭。我们的研究结果表明，COL4A3 和 NPHS2 可能对 FSGS 引起的肾损伤具有协同作用。进一步分析肾小球滤过屏障有助于评估肾脏损伤的原因。此外，对肾小球基底膜相关基因和足细胞结构蛋白的详细分析可以帮助我们更好地了解 FSGS 的发病机制，并为遗传性肾小球疾病的预后和治疗提供新的见解。
