Monogenetic causes of nephrotic syndrome

Steroid-resistant nephrotic syndrome (SRNS) represents a frequent cause of end-stage renal disease in children. Renal histology shows focal segmental glomerulosclerosis in about 80% of cases. Recently, it became apparent that up to 28% of all cases of childhood nephrotic syndrome are caused by recessive mutations of podocin (NPHS2). Additional monogenic causes are mutations of nephrin (NPHS1), WT1, PLCE1, or LAMB2. The related gene products are expressed in the glomerular podocyte and are essential for development and maintenance of the glomerular filtration barrier. These genetic insights have led to a better understanding of the pathogenesis of SRNS and will allow for unequivocal molecular genetic diagnostics and for stratification in therapeutic studies.