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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Proteins / genetics
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins*
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Cloning, Molecular
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DNA Mutational Analysis
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Expressed Sequence Tags
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Fetus
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Genes, Recessive
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Genetic Linkage
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Helminth Proteins / genetics
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Humans
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In Situ Hybridization
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Intracellular Signaling Peptides and Proteins
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Kidney Glomerulus / embryology
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Kidney Glomerulus / metabolism*
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Membrane Proteins / genetics*
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Molecular Sequence Data
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Multigene Family
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Mutation / genetics*
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Nephrotic Syndrome / genetics*
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Nephrotic Syndrome / metabolism
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Organ Specificity
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Pedigree
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Physical Chromosome Mapping
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
Substances
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Blood Proteins
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Caenorhabditis elegans Proteins
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Helminth Proteins
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Intracellular Signaling Peptides and Proteins
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MEC-2 protein, C elegans
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Membrane Proteins
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NPHS2 protein
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STOM protein, human
Associated data
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GENBANK/AJ279246
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GENBANK/AJ279247
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GENBANK/AJ279248
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GENBANK/AJ279249
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GENBANK/AJ279250
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GENBANK/AJ279251
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GENBANK/AJ279252
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GENBANK/AJ279253
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GENBANK/AJ279254