伴肾小球薄基膜改变的IgA肾病非胶原Ⅳ基因变异分析  

Analysis of non-collagenⅣgene variation in IgA nephropathy with glomerular thin basement membrane changes

作　　者：徐华[1] 余学问[1] 梁莹莹 李芸[2] 曾又佳[2] 张露 徐洲稳 李霞[1] 邵牧民[1] XU Hua;YU Xue-wen;LIANG Ying-ying;LI Yun;ZENG You-jia;ZHANG Lu;XU Zhou-wen;LI Xia;SHAO Mu-min(Department of Pathology,Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518033,China;Department of Nephrology,the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine,Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518033,China)

机构地区：[1]广州中医药大学第四临床医学院/深圳市中医院病理科,深圳518033 [2]广州中医药大学第四临床医学院/深圳市中医院肾病科,深圳518033

出　　处：《临床与实验病理学杂志》2022年第10期1153-1158,共6页Chinese Journal of Clinical and Experimental Pathology

基　　金：广东省医学科学技术研究基金(A2019265)。

摘　　要：目的探讨伴薄基膜改变的IgA肾病中非胶原Ⅳ基因变异意义及临床病理特征。方法提取6例伴薄基膜改变的IgA肾病患者的外周血单个核细胞总DNA,通过全外显子组测序技术检测基因变异情况,并采用Sanger测序进行验证,对候选变异基因进行生物信息学功能分析;收集患者临床及实验室检查信息,分析临床表现及特点;采用HE、免疫组化及免疫荧光法对伴薄基膜改变的IgA肾病进行检测,观察患者肾脏穿刺组织病理学特征。结果6例样本中2例发现FN1基因变异(c.3289G>A和c.4616C>G),同时还分别存在NUP160(c.160G>A)和ITGA3(c.3046-4G>A)基因变异;其中FN1变异为可能致病性变异,NUP160、ITGA3变异为意义未明变异。2例患者均为年轻女性,临床表现为血尿及非肾病综合征范围蛋白尿,早期肾功能正常,均伴有皮疹。病理形态学为局灶节段性硬化及轻度系膜增生,系膜区可见电子致密物沉积,基膜均质变薄,足细胞不同程度微绒毛活化及足突融合,坏死或新月体不常见。结论伴薄基膜改变的IgA肾病中存在FN1、NUP160、ITGA3等非胶原Ⅳ基因变异,该类患者具有皮疹等独特的临床和病理学特征。丰富了伴薄基膜改变的IgA肾病中非胶原Ⅳ的候选变异基因谱及FN1相关肾病的疾病表型谱;NUP160、ITGA3可能是对此类疾病蛋白尿起协同作用的基因变异。Purpose To investigate the significance of non-collagenⅣgene variation and clinicopathological features in IgA nephropathy with thin basement membrane changes.Methods Total DNA was extracted from peripheral blood mononuclear cells of 6 patients with IgA nephropathy with thin basement membrane changes.Gene variation was detected by whole exome sequencing and verified by Sanger sequencing.Bioinformatics function analysis of candidate mutation genes was performed.The clinical characteristics of patients were analyzed by collecting the clinical and laboratory examination information,and the pathomorphological characteristics were observed by HE,immunohistochemistry and immunofluorescence staining in renal biopsy slides.Results FN1 gene variation was found in 2 patients(c.3289G>A and c.4616C>G)and NUP160(c.160G>A)and ITGA3(c.3046-4G>A)genetic variation.Among them,the variation of FN1 was probably pathogenic,NUP160 and ITGA3 were uncertain significance.Both patients were young women with clinical manifestations of hematuria and proteinuria(non nephrotic syndrome),normal renal function,and a relatively special manifestation of rash.The pathologic features were focal segmental sclerosis and mild mesangial hyperplasia,deposition of electron dense material in mesangial area,thinning of homogeneous basement membrane,activation of microvilli of podocytes and fusion of foot processes to varying degrees,necrosis and crescent were uncommon.Conclusion The present study is the first to report FN1,NUP160,and ITGA3 gene mutations in IgA nephropathy with thin basement membrane changes,with distinctive clinical and pathological features such as rash.The FN1 variant enriches the candidate variant gene spectrum of non collagenⅣin IgA nephropathy with thin basement membrane changes and the disease phenotype spectrum of FN1 related nephropathy.There are also gene variants(NUP160 and ITGA3)that may have synergistic effect on proteinuria in this disease.

关 键 词：IGA肾病 薄基膜 基因变异 FN1 NUP160 ITGA3 

分 类 号：R692.6[医药卫生—泌尿科学]