Secondary focal and segmental glomerulosclerosis associated with single-nucleotide polymorphisms in the genes encoding complement factor H and C3.
Secondary focal and segmental glomerulosclerosis associated with single-nucleotide polymorphisms in the genes encoding complement factor H and C3.
复制标题
DOI：
10.1053/j.ajkd.2012.04.011
复制
发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Smith RJ
中科院分区：
文献类型：
--
作者：
Sethi S;Fervenza FC;Zhang Y;Smith RJ
局灶性节段性肾小球硬化（FSGS）的遗传原因通常涉及足细胞或肾小球基底膜（更罕见）中表达的基因突变和等位基因变体。在这份报告中，我们描述了一个60岁的女性慢性肾脏疾病，其肾脏活检显示FSGS。免疫荧光研究中未检测到免疫球蛋白和C3。电子显微镜检查显示内皮下蓬松颗粒状物质，偶见双轮廓形成，提示毛细血管壁损伤，提示血栓前状态。对补体旁路途径的评估揭示了补体因子H短共有重复序列（SCR）12（CFH; c.2195C>T，p.Thr732Met）和补体因子C3（c.463A>C，p.Lys155Gln）中一种新的多态性，该多态性以前曾报道过，但在很大程度上未被表征。旁路途径的失调与非典型溶血综合征（阿胡斯）和致密存款病有关，但迄今为止与FSGS无关。该病例强调了补体介导的肾小球疾病的范围扩大，并表明具有毛细血管壁损伤特征的FSGS应提示评估旁路途径的异常。该病例还扩展了与FSGS表型相关的遗传多态性列表。
Genetic causes of focal and segmental glomerulosclerosis (FSGS) typically involve mutations and allele variants of genes expressed in podocytes or, more rarely, in glomerular basement membranes. In this report, we describe a 60-year-old woman with chronic kidney disease whose kidney biopsy showed FSGS. Immunoglobulins and C3 were undetectable in immunofluorescence studies. Electron microscopy showed subendothelial fluffy granular material with occasional double contour formation suggestive of capillary wall injury, and prompting work-up for a prothrombotic state. Evaluation of the alternative pathway of complement revealed a novel polymorphism in short consensus repeat (SCR) 12 of complement factor H (CFH; c.2195C>T, p.Thr732Met) and a previously reported but largely uncharacterized polymorphism in complement factor C3 (c.463A>C, p.Lys155Gln). Dysregulation of the alternative pathway is associated with atypical hemolytic syndrome (aHUS) and Dense Deposit Disease, but heretofore has not been associated with FSGS. This case highlights the expanding spectrum of complement-mediated glomerular disease, and shows that FSGS with features of capillary wall injury should prompt evaluation for abnormalities in the alternative pathway. This case also expands the list of genetic polymorphisms that can be associated with an FSGS phenotype.
登录
查看更多内容
影响因子：
4
作者：
Servais, Aude;Fremeaux-Bacchi, Veronique;Fakhouri, Fadi
通讯作者：
Fakhouri, Fadi
人类层粘连蛋白β2缺乏症会导致伴有间质硬化的先天性肾病和明显的眼部畸形
影响因子：
3.5
作者：
Zenker, M;Aigner, T;Reis, A
通讯作者：
Reis, A
影响因子：
19.6
作者：
通讯作者：
--
影响因子：
13.6
作者：
Smith, Richard J. H.;Alexander, Jessy;Zipfel, Peter F.
通讯作者：
Zipfel, Peter F.
影响因子：
19.6
作者：
Santin, Sheila;Garcia-Maset, Rafael;Torra, Roser
通讯作者：
Torra, Roser