Focal and segmental glomerulosclerosis (FSGS) is a common pattern of renal injury. This injury pattern is observed in patients with idiopathic proteinuria, in association with various forms of primary renal injury, and can be the pattern of injury seen in highly penetrant inherited forms of kidney disease. In the last decade, several loci have been identified in families affected with FSGS by genetic linkage analysis. Rare deleteroious mutations that segregate with disease have subsequently been identified from fine mapping the regions identified by these methods in NPHS2 (at chr1q25-q31) [1], ACTN4 (chr19q13) [2], TRPC6 (chr11q21-q22) [3,4] and PLCE1 (chr10q23) [5]. NPHS2 mutations are responsible for a non-trivial fraction of pediatric FSGS and steroid-resistant nephrotics syndrome, but only a small percentage of adult-onset disease. Coding-region variation in the other genes mentioned explain disease in very few patients with ‘sporadic’ non-familial FSGS[6,7,8,9,10,11,12].
