Idiopathic nephrotic syndrome may have two underlying mechanisms: either (1) an alteration of the immune system resulting in the production of a putative circulating factor of glomerular permeability; or (2) mutations in the structural genes of the glomerular filtration barrier in which case patients are typically multidrug resistant and do not recur after transplantation. The latter forms have been recently recognized as “hereditary podocytopathies.” In the past few years, positional cloning approaches that allow the identification of gene mutations underlying diseases whose pathophysiology is unknown and animal models have helped decipher the pathophysiological mechanisms of the glomerular filtration process. Recently, the advent of next-generation sequencing (NGS) techniques has greatly facilitated the identification of numerous novel causative genes in hereditary podocytopathies. Moreover, it has revealed mutations in unexpected genes and has widened the phenotypes associated with podocyte gene mutations. The list of genes mutated in hereditary podocytopathies is constantly evolving and consists to date of more than 40 genes. However, the most recently identified genes are extremely rarely mutated and may concern only a couple of families worldwide. These discoveries provided crucial insight into the pathophysiological mechanisms linking podocyte proteins to kidney function. This review will focus on monogenic podocytopathies affecting adult patients.

Keywords:
Familial nephrotic syndrome, Genetics, Steroid resistance, Podocyte, Next-generation sequencing
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