Yu Zihua, Ding Jie, Guan Na, Shi Yan, Zhang Jingjing, Huang Jianping, Yao Yong, Yang Jiyun
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Pediatr Nephrol. 2004 Nov;19(11):1285-9. doi: 10.1007/s00467-004-1585-y.
Since the identification of the NPHS2 gene,which encodes podocin, several groups from European, Middle Eastern, and North American countries have reported NPHS2 mutations in families with steroid-resistant nephrotic syndrome (SRNS) or focal segmental glomerulo sclerosis (FSGS). Families with SRNS have also been reported in China with a population of more than1.3 billion. However, to our knowledge, there is no mutational analysis of the NPHS2 gene in familial SRNS orFSGS in China. We identified a novel mutation of NPHS2(467_468insT and 503G>A) in a Chinese family with autosomal recessive SRNS using polymerase chain re-action, denaturing high-performance liquid chromatography, and DNA sequencing techniques. The results demonstrate that there is also NPHS2 mutation in Chinese familial SRNS. Therefore, Chinese SRNS patients with a familial history of NS should also be screened for possible mutations of NPHS2. We also detected clearly decreased staining with a specific podocin C-terminal antibody(P35) and negative staining with a specific podocin N-terminal antibody (P21). These results were contrary to those predicted from the mutated sites. Further studies are needed to explore the mechanism and impact of the mutant gene on the expression and localization of the relevant protein.
自从编码足突蛋白的NPHS2基因被鉴定出来后，来自欧洲、中东和北美国家的多个研究小组报告了在患有激素抵抗性肾病综合征（SRNS）或局灶节段性肾小球硬化症（FSGS）的家族中存在NPHS2突变。在中国这个拥有超过13亿人口的国家，也有关于SRNS家族的报道。然而，据我们所知，中国尚未对家族性SRNS或FSGS中的NPHS2基因进行突变分析。我们使用聚合酶链反应、变性高效液相色谱和DNA测序技术，在中国一个患有常染色体隐性SRNS的家族中鉴定出一种新的NPHS2突变（467_468insT和503G>A）。结果表明，中国家族性SRNS中也存在NPHS2突变。因此，有肾病家族史的中国SRNS患者也应筛查是否存在NPHS2的可能突变。我们还清楚地检测到用特异性足突蛋白C末端抗体（P35）染色减少，以及用特异性足突蛋白N末端抗体（P21）染色呈阴性。这些结果与从突变位点预测的结果相反。需要进一步研究来探索突变基因对相关蛋白质表达和定位的机制及影响。
