PDF(Pubmed)
Abstract：
This study highlights the importance of a combined diagnostic approach in the diagnosis of rare diseases, such as adult-onset genetic FSGS. We present three adult patient cases evaluated with kidney biopsy for proteinuria, chronic kidney disease, and hypertension, which were suggestive of adult-onset genetic FSGS. Renal biopsy samples and formalin-fixed, paraffin-embedded fetal kidneys were evaluated using standard light microscopical stainings, direct immunofluorescence on cryostat sections, and electron microscopy. Clinical exome sequencing was performed for each case, and 45 FSGS-related genes were analyzed. Identifying mutations in the PAX2, ACTN4, and COL4A5 genes have prompted a re-evaluation of the previous histopathological examinations. The PAX2 mutation led to a thinner nephrogenic zone and decreased number of glomeruli, resulting in oligohydramnios during fetal development and oligomeganephronia and adaptive focal-segmental glomerulosclerosis in adulthood. The ACTN4 mutation caused distinct electron-dense aggregates in podocyte cell bodies, while the COL4A5 mutation led to segmental sclerosis of glomeruli with marked interstitial fibrosis and tubular atrophy. The identification of specific mutations and their histopathological consequences can lead to a better understanding of the disease and its progression, as well as potential treatment options.
摘要：
这项研究强调了联合诊断方法在罕见疾病诊断中的重要性。例如成人发病的遗传FSGS。我们介绍了3例成人患者的蛋白尿肾活检评估，慢性肾病,和高血压，提示成人发病的遗传性FSGS。肾活检样本和福尔马林固定，使用标准光学显微镜染色评估石蜡包埋的胎儿肾脏，在低温恒温器切片上的直接免疫荧光，和电子显微镜。对每个病例进行临床外显子组测序，分析了45个FSGS相关基因。鉴定PAX2，ACTN4和COL4A5基因中的突变促使对先前的组织病理学检查进行重新评估。PAX2突变导致较薄的肾原区和肾小球数量减少，导致胎儿发育过程中羊水过少，成年期出现少张性肾小球硬化和适应性局灶性节段肾小球硬化。ACTN4突变导致足细胞细胞体中不同的电子致密聚集体，而COL4A5突变导致肾小球节段性硬化，伴有明显的间质纤维化和肾小管萎缩。识别特定突变及其组织病理学后果可以更好地了解疾病及其进展，以及潜在的治疗选择。
