Genotypic and Phenotypic Features of Both NPHS1 and NPHS2 Genes in Infantile Nephrotic Syndrome and Prognostic Effect of E117K Polymorphism in NPHS1 Gene

Abstract

Background: Infantile nephrotic syndrome (INS) refers to disease that is present after the first three months of life up to one year of age. There is genetic heterogeneity and genotype-phenotype correlation is not clear. Objectives: The focus of the present study was to analyze genotypic and phenotypic features of both NPHS1 and NPHS2 genes in INS. Methods: Clinical data, mutational analysis, histology, treatments, and outcomes of 48 children with NS are evaluated. A direct sequencing of NPHS1 gene and NPHS2 gene was performed. Patients were classified into 3 groups; group 1: cases having only NPHS1 mutation; group 2: cases with only NPHS2 mutation; group 3: cases without any mutation. Results: The mean age at onset of the disease was 8.7 ± 2.3 months, and mean follow-up time was 8.3 years. Seven familial and 41 sporadic cases of INS were found. Kidney biopsy was performed in 45 out of 48 patients and pathological investigations revealed focal segmental glomerulosclerosis in 29 (65%), IgM nephropathy in 6 (13%), and minimal change disease in 10 patients (22%). There were 5 (10.4%) cases in group 1 (patients having only mutations of NPHS1) and 13 cases (27%) in group 2 (patients having only mutations of NPHS2). Thirty cases (62.5%) had neither NPHS1 nor NPHS2 mutation (group 3). Conclusions: The genotypic and phenotypic features of INS were demonstrated. We found that INS with podocin mutation has poor prognosis according to exonal distribution. NPHS1 mutations caused a severe disease but with a more favorable prognosis.