Molecular genetic studies on pathogenesis and mechanism of progression for focal segmental glomerulosclerosis in Children

背景资料。NPHS2基因突变与常染色体隐性遗传性激素抵抗型肾病综合征相关，以儿童早期蛋白尿、局灶性节段性肾小球硬化(FSGS)和快速进展为终末期肾病(ESRD)为特征。我们分析了FSGS患者的NPHS2基因。我们制备了兔抗人Podocin偶联肽的多克隆抗体，并利用正常人和FSGs患者的肾组织对Podocin进行了研究。结果与结论在6例家族性FSGS或FSGS进展为ESRD的患者中未发现任何突变。免疫组织化学显示，Podocin沿肾小球毛细血管环呈线性分布。在大多数FSGS受试者(70%)中，Podocin要么减少要么缺失。在7例缺乏podocin表达的FSGS患者中，2例(20%)进展为ESRD。我们认为，Podocin表达缺失可能是预后不良的原因。

Background. Mutations of NPHS2 are associated with autosomal recessive steroid-resistant nephrotic syndrome, which is characterized by early childhood onset of proteinuria, focal segmental glomerulosclerosis (FSGS) and rapid progression to end-stage renal disease (ESRD).Methods. We analyzed the NPHS2 gene in patients with FSGS. We generated rabbit polyclonal antibodies against conjugated peptides from human podocin, and studied podocin using kidney tissues of normal humans and those with FSGS.Results and Conclusions. We did not find any mutation in 6 patients with familial FSGS or FSGS progressive to ESRD. Immuno-histochemically, podocin was detected in a linear pattern along the glomerular capillary loop. Podocin was either decreased or absent in most subjects (70%) with FSGS. Of seven FSGS patients with absence of podocin expression, two (20%) progressed to ESRD. We propose that absence of podocin expression may be bad prognosis.