[A genetic viewpoint of focal glomerular sclerosis: fom genes to glomerular pathophysiology [corrected]]

Recent studies of Mendelian disease have begun to clarify the clinical spectrum of the group of disorders that make up familial, focal segmental glomerulosclerosis (FSGS) and nephrotic syndromes. In familial forms of focal segmental glomerulosclerosis (FSGS), both autosomal recessive and dominant inheritance patterns have been reported. At least three genes have been identified which, when defective, cause familial FSGS or nephrosis: the NPHS1 gene, encoding nephrin; the NPHS2 gene, encoding podocin; and the ACTN4 gene, encoding a-actinin-4. Because the majority of FSGS cases occur as sporadic disease, the recently described mutations in the NPHS2 gene "in approximately 25 percent of cases of apparently sporadic, steroid-resistant FSGS in children" have claimed great interest. The applicability of these observations to adults, including the possible importance of the nephrin and alpha-actinin-4 genes in the sporadic disease, remain to be determined. Finally, the mechanisms of podocyte damage and the molecular basis of glomerulosclerosis are reviewed.