Mutational analysis of podocyte genes in children with sporadic steroid-resistant nephrotic syndrome.

Abstract

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.