title: NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome.
abstract: Familial idiopathic nephrotic syndromes represent a heterogeneous group of kidney disorders, and include autosomal recessive steroid-resistant nephrotic syndrome, which is characterized by early childhood onset of proteinuria, rapid progression to end-stage renal disease and focal segmental glomerulosclerosis. A causative gene for this disease, NPHS2, was mapped to 1q25-31 and we report here its identification by positional cloning. NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family. We found ten different NPHS2 mutations, comprising nonsense, frameshift and missense mutations, to segregate with the disease, demonstrating a crucial role for podocin in the function of the glomerular filtration barrier.
authors.affiliation: Inserm U423, Tour Lavoisier, Université René Descartes, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Boute
authors.forename: O
authors.initials: O
authors.lastname: Gribouval
authors.forename: S
authors.initials: S
authors.lastname: Roselli
authors.forename: F
authors.initials: F
authors.lastname: Benessy
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Fuchshuber
authors.forename: K
authors.initials: K
authors.lastname: Dahan
authors.forename: M C
authors.initials: MC
authors.lastname: Gubler
authors.forename: P
authors.initials: P
authors.lastname: Niaudet
authors.forename: C
authors.initials: C
authors.lastname: Antignac
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000235:genetics; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D020224:Expressed Sequence Tags; D005333:Fetus; D005808:Genes, Recessive; D008040:Genetic Linkage; D015801:Helminth Proteins / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D007678:Kidney Glomerulus / Q000196:embryology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation / Q000235:genetics*; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D010375:Pedigree; D020161:Physical Chromosome Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D001798:Blood Proteins; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D047908:Intracellular Signaling Peptides and Proteins; C096705:MEC-2 protein, C elegans; D008565:Membrane Proteins; C407223:NPHS2 protein; C036860:STOM protein, human