散发性激素耐药型肾病综合征患儿30例足细胞基因突变分析

目的分析散发性激素耐药型肾病综合征(SRNS)儿童足细胞基因突变及其特点。方法研究对象为30例散发性SRNS患儿和50例尿检正常的健康志愿者。采用PCR扩增NPHS1、NPHS2和CD2AP基因全部外显子及其周围的部分内含子,WT1基因外显子8和9及其周围的部分内含子;应用DNA序列直接测定法对其PCR产物进行测序。结果在10例应用激素和免疫抑制剂治疗肾病无缓解的SRNS患儿中,发现1例携带WT1基因杂合突变——1180C>T(R394W),1例携带NPHS1基因复合杂合突变——2677A>G(T893A)和*142T>C,1例携带CD2AP基因杂合突变IVS13-137G>A。在20例应用激素或免疫抑制剂治疗肾病缓解的SRNS患儿中,发现4例患儿携带NPHS1基因单杂合突变——928G>A、IVS8+30C>T、IVS21+14G>A和IVS25-23C>T,1例患儿携带CD2AP基因单杂合突变(IVS7-135G>A)。结论对激素和免疫抑制剂均耐药的SRNS患儿需进行足细胞基因突变分析。

Mutational Analysis of Podocyte Genes in 30 Chinese Children with Sporadic Steroid-Resistant Nephrotic Syndrome

Objective To examine mutations in podocyte genes in Chinese children with sporadic steroid-resistant nephrotic syndrome(SRNS). Methods Mutational analysis was performed by means of polymerase chain reaction and directly sequencing for all exons and exon-intron boundaries podocyte genes of NPHS1,NPHS2 and CD2AP as well as exons 8,9 and exon-intron boundaries of WT1 in 30 Chinese children with sporadic SRNS and 50 healthy volunteers whose urinalysis were normal. Results Among 10 SRNS patients with no response to the therapy consisting of steroid and immunosuppressive agents,1 patient showed a heterozygous mutation in the WT1 gene,1180C>T(R394W),1 patient showed compound heterozygous NPHS1 mutations,2677A>G(T893A) and *142T>C,and 1 patient showed a heterozygous mutation in the CD2AP gene,IVS13-137G>A.Of 20 patients with a complete remission responding to prolonged steroid treatment of immunosuppressive agents,4 heterozygous NPHS1 mutations,928G>A,IVS8+30C>T,IVS21+14G>A and IVS25-23C>T were detected in 4 patients,respectively,and a heterozygous CD2AP mutation,IVS7-135G>A was found in 1 case. Conclusion It suggests that mutatio-nal analysis of the podocyte should be performed in Chinese children with no response to both steroid and immunosuppressive agents.