Wang Hairong, Wang Lihui, Wen Lu, Wang Haixia, Wang Fengjuan
Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Aug 10;41(8):931-935. doi: 10.3760/cma.j.cn511374-20231019-00205.
To explore the genetic basis and clinical phenotype of a Chinese pedigree affected with Focal segmental glomerulosclerosis (FSGS).
A male patient who was admitted to the First Affiliated Hospital of Zhengzhou University on July 26, 2018 was selected as the study subject. Clinical data of the patient was collected. Next generation sequencing and Sanger sequencing were carried out to detect the variant sites. Bioinformatic software was used to simulate the effect of candidate variant on the protein functions.
Ultrasound exam of the patient showed enhanced echo for the renal parenchyma. Kidney biopsy had confirmed the pathological diagnosis of FSGS (non-specific). Electronic microscopy displayed segmental sclerosis of the glomeruli, mild hyperplasia of mesangial cells and matrix. The proband was found to harbor two novel variants of the PLCE1 gene, namely c.3199delA (p.N1067Mfs*15) and c.4441_4443delATC (p.1481_1481del), which were respectively inherited from his mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PM2_Supporting+PP3; PM2_Supporting+PM3+PP3). Bioinformatic simulation suggested that both variants could significantly affect the tertiary structure of the PLCE1 protein.
The c.4441_4443delATC and c.3199delA variants of the PLCE1 gene probably underlay the pathogenesis of the FSGS in this pedigree.
探究一个患局灶节段性肾小球硬化（FSGS）的中国家系的遗传基础和临床表型。
选取2018年7月26日入住郑州大学第一附属医院的一名男性患者作为研究对象。收集该患者的临床资料。采用二代测序和桑格测序检测变异位点。使用生物信息学软件模拟候选变异对蛋白质功能的影响。
患者超声检查显示肾实质回声增强。肾活检确诊为FSGS（非特异性）。电子显微镜显示肾小球节段性硬化，系膜细胞和基质轻度增生。先证者被发现携带PLCE1基因的两个新变异，即c.3199delA（p.N1067Mfs*15）和c.4441_4443delATC（p.1481_1481del），分别遗传自他的母亲和父亲。根据美国医学遗传学与基因组学学会（ACMG）的指南，这两个变异均被评为致病性变异（PVS1+PM2_支持+PP3；PM2_支持+PM3+PP3）。生物信息学模拟表明这两个变异均可显著影响PLCE1蛋白的三级结构。
PLCE1基因的c.4441_4443delATC和c.3199delA变异可能是该家系FSGS发病机制的基础。
