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目的:探讨 PLCE1基因变异所致的1例局灶节段性肾小球硬化(FSGS)患儿的临床表现和基因变异特点。 方法:选取2018年7月26日就诊于郑州大学第一附属医院的1例局灶节段性肾小球硬化男性患儿作为研究对象，收集其临床资料，采用高通量测序和Sanger测序技术分析其变异位点，用生物信息学软件分析模拟变异位点对蛋白活性的影响。结果:患儿为1岁男性，肾脏超声提示双肾实质回声增强，病理诊断为局灶节段性肾小球硬化症(非特殊性)样病变；电镜检查显示肾小球节段性硬化，小球系膜细胞和基质轻度增生。患儿 PLCE1基因存在母源c.3199delA (p.N1067Mfs*15)和父源c.4441_4443delATC (p.1481_1481del)复合杂合变异。根据美国医学遗传学与基因组学学会的相关指南，二者均被判定为致病性变异(PVS1＋PM2_Supporting＋PP3；PM2_Supporting＋PM3＋PP3)。蛋白模拟提示二者均对PLCE1蛋白质的三级结构产生了显著的影响。 结论:PLCE1基因c.3199delA (p.N1067Mfs*15)和c.4441_4443delATC (p.1481_1481del)复合杂合变异可能是该患儿FSGS的遗传学病因。

Objective:To explore the genetic basis and clinical phenotype of a Chinese pedigree affected with Focal segmental glomerulosclerosis (FSGS).Methods: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 variants on the protein functions.Results: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. Conclusion:The c. 4441_4443delATC and c. 3199delA variants of the PLCE1 gene probably underlay the pathogenesis of the FSGS in this pedigree.