Feng D N, Yang Y H, Wang D J, Meng D C, Fu R, Wang J J, Yu Z H
Department of Pediatrics, Fuzhou Dongfang Hospital, Fuzhou, Fujian, China.
Department of Pediatrics, Fuzhou Dongfang Hospital, Fuzhou, Fujian, China
Genet Mol Res. 2014 Nov 11;13(4):9514-22. doi: 10.4238/2014.November.11.16.
Recent studies have demonstrated that mutations in 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1, are associated with the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). Systematic investigation of all 4 genes for sporadic SRNS in China has not been performed. We examined 10 Chinese children with sporadic SRNS who showed no response to immunosuppressive agents and 20 SRNS controls who exhibited a response to prolonged steroid or immunosuppressive treatment and achieved complete remission. We analyzed mutations in the 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1. Mutational analysis was performed using polymerase chain reaction and direct sequencing. Of the 10 SRNS children who showed no response to immunosuppressive agents, the compound heterozygous NPHS1 mutations 2677A>G (T893A) and *142T>C were identified in 1 patient, while a heterozygous mutation in WT1, 1180C>T (R394W), was found in another patient. Of the 20 SRNS children showing complete remission who responded to prolonged steroid therapy or immunosuppressive agents, 4 heterozygous NPHS1 mutations, 928G>A, IVS8+30C>T, IVS21+14G>A, and IVS25-23C>T, were identified in 4 patients and a heterozygous CD2AP mutation, IVS7-135G>A, was identified in 1 patient. Our results indicate the necessity of genetic examination for mutations in podocyte genes in Chinese SRNS children who show no response to immunosuppressive agents.
近期研究表明，足细胞相关的4个基因（NPHS1、NPHS2、CD2AP和WT1）的突变与激素抵抗型肾病综合征（SRNS）的发病机制相关。在中国，尚未对散发性SRNS的所有这4个基因进行系统研究。我们检查了10名对免疫抑制剂无反应的中国散发性SRNS儿童以及20名对延长激素或免疫抑制治疗有反应并实现完全缓解的SRNS对照儿童。我们分析了4个足细胞基因（NPHS1、NPHS2、CD2AP和WT1）中的突变。采用聚合酶链反应和直接测序进行突变分析。在10名对免疫抑制剂无反应的SRNS儿童中，1例患者检测到复合杂合NPHS1突变2677A>G（T893A）和*142T>C，而另1例患者检测到WT1杂合突变1180C>T（R394W）。在20名对延长激素治疗或免疫抑制剂有反应并实现完全缓解的SRNS儿童中，4例患者检测到4种NPHS1杂合突变，即928G>A、IVS8+30C>T、IVS21+14G>A和IVS25-23C>T，1例患者检测到CD2AP杂合突变IVS7-135G>A。我们的结果表明，对于对免疫抑制剂无反应的中国SRNS儿童，有必要进行足细胞基因突变的基因检测。
