Genetics in Clinical Practice: Nephrotic and Proteinuric Syndromes

Abstract

Nephrotic syndrome (NS) is a disorder of the glomerular filtration barrier, a highly specialised tri-layer structure with unique functional properties. Recent advances emanating from the field of molecular genetics have revealed the podocyte as probably the central player in the control of glomerular filtration. More specifically, the cell–cell junction between adjacent podocyte foot processes, the slit diaphragm, has been revealed to be made up of a sophisticated multi-protein complex which dynamically controls foot process architecture via signalling to the actin cytoskeleton. Key genes that have been identified from the study of inherited NS include those encoding nephrin, podocin, TRPC6 and α-actinin-4, and more remain to be found. It is now possible to identify genetic causes underlying a proportion of NS presenting at any age, and this review aims to help describe genetic NS according to age of presentation, and provide information on known mutations. The next big challenge for clinicians and researchers is to translate the molecular information learnt into the understanding of acquired, non-inherited forms of the disease.