The aims of this study were to identify the genetic mutations profile in Brazilian children with nephrotic syndrome (NS) and to determine a genotype-phenotype correlation in this disease.Methods
Next-generation sequencing and mutation analysis were performed on 24 genes related to NS in a cross-sectional study involving 95 children who underwent kidney transplantation due to NS, excluding congenital cases.Results
A total of 149 variants were identified in 22 of 24 sequenced genes. The mutations were classified as pathogenic, likely pathogenic, likely benign and benign per the chance of causing the disease. NPHS2 was the most common mutated gene. We identified 8 (8.4%) patients with hereditary NS and 5 (5%) patients with probably genetically caused NS. COL4A3-5 variants were found as well, but it is not clear whether they should be considered isolated FSGS or simply a misdiagnosed type of the Alport spectrum. Considering the clinical results, hereditary NS patients presented a tendency to early disease onset when compared with the other groups (P = 0.06) and time to end stage renal disease (ESRD) was longer in this group (P = 0.03). No patients from hereditary NS group had NS recurrence after transplantation.Conclusions
This is the first study in children with steroid-resistant NS who underwent kidney transplantation using next-generation sequencing. Considering our results, we believe this study has shed some light to the uncertainties of genotype-phenotype correlation in NS, where several genes cooperate to produce or even to modify the course of the disease.