Background: In the past few years, genetic studies of familial steroid-resistant nephrotic syndrome and generation of murine models of these diseases have resulted in tremendous progress in the understanding of the physiology and pathology of podocyte

Data sources: Based on recent original publications and the experience with the disease of our group, we review the different genetic forms of autosomal recessive and dominant nephrotic syndrome, and  indicate the possible, cellular and functional consequences of the gene defects.

Results: The major role of the glomerular slit diaphragm in the formation and the maintenance of the glomerular ultrafiltration barrier has been demonstrated. This knowledge has improved the diagnosis and management of steroid-resistant nephrotic syndromes, especially in children. Familial nephrotic syndrome is characterized by clinical and genetic heterogeneneity, but most histological lesions are non-specific.

Conclusions: The recognition of the genetic origin of the disease and, if possible, the detection of the resultant mutation are useful clinically. They allow to avoid unnecessary and aggressive immunosuppressive treatments, to predict the absence of recurrence after transplantation, and to provide prenatal diagnosis to families at risk.

Key words: podocyte; hereditary nephrotic syndromes; NPHS1; NPHS2; WT1