title: The genetic basis of FSGS and steroid-resistant nephrosis.
abstract: Studies of Mendelian forms of focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome have provided new insights into the mechanism of these diseases. Congenital nephrotic syndrome and familial forms of FSGS form a spectrum of podocyte diseases of varying severity and age of onset. Mutations in both nephrin gene (NPHS1) alleles lead to congenital nephrosis, podocyte foot process efacement, and loss of slit-diaphragm structure. Mutations in both podocin gene (NPHS2) alleles lead to a wide range of human disease, from childhood-onset steroid-resistant FSGS and minimal change disease to adult-onset FSGS. Dominantly inherited mutations in ACTN4, the alpha-actinin-4 gene, can lead to a slowly progressive adult-onset form of FSGS. In addition, FSGS is observed as part of several rare multisystem inherited syndromes. Here we review recent progress in understanding the genetic basis of FSGS in humans.
authors.affiliation: Renal Division, Brigham and Women's Hospital, 77 Louis Pasteur Ave, Boston, MA, USA. mpollak@rics.bwh.harvard.edu
authors.forename: Martin R
authors.initials: MR
authors.lastname: Pollak
mesh_terms: D000818:Animals; D004351:Drug Resistance / Q000235:genetics*; D004847:Epithelial Cells / Q000473:pathology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007678:Kidney Glomerulus / Q000166:cytology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D009401:Nephrosis / Q000188:drug therapy* / Q000235:genetics*; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D011506:Proteins / Q000235:genetics; D013256:Steroids / Q000627:therapeutic use*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D011506:Proteins; D013256:Steroids; C113267:nephrin