nephrin and Hypoproteinemia

Congenital nephrotic syndrome of the Finnish type is a serious renal disease belonging to the Finnish disease heritage. It appears as substantial proteinuria, hypoproteinemia and edema in a newborn. Kidney transplantation is the only effective treatment. The cause of the disease is a mutation in the gene encoding the nephrin protein. Nephrin is produced by the epithelial cell (podocyte) of the glomerulus. It is expressed in the slit membrane connecting the pedicles of the podocyte. This finding has revolutionized the concept of glomerular filtration and set off active research on the pathogenetic mechanisms of proteinuria.

Topics: Edema; Finland; Genotype; Glomerular Filtration Rate; Humans; Hypoproteinemia; Infant, Newborn; Kidney Transplantation; Membrane Proteins; Mutation; Nephrotic Syndrome; Proteinuria

Congenital nephrotic syndrome (NPHS1) is a rare disease inherited as an autosomally recessive trait. The NPHS1 gene mutated in NPHS1 children has recently been identified. The gene codes for nephrin, a cell-surface protein of podocytes. Two mutations, named Fin-major and Fin-minor, have been found in over 90% of the Finnish patients. In this study, we correlated the NPHS1 gene mutations to the clinical features and renal findings in 46 Finnish NPHS1 children.. Clinical data were collected from patient files, and kidney histology and electron microscopy samples were re-evaluated. The expression of nephrin was studied using immunohistochemistry, Western blotting, and in situ hybridization.. Nephrotic syndrome was detected in most patients within days after birth regardless of the genotype detected. No difference could be found in neonatal, renal, cardiac, or neurological features in patients with different mutations. Nephrin was not expressed in kidneys with Fin-major or Fin-minor mutations, while another slit diaphragm-associated protein, ZO-1, stained normally. In electron microscopy, podocyte fusion and podocyte filtration slits of various sizes were detected. The slit diaphragms, however, were missing. In contrast to this, a nephrotic infant with Fin-major/R743C genotype expressed nephrin in kidney had normal slit diaphragms and responded to therapy with an angiotensin-converting enzyme inhibitor and indomethacin.. The most common NPHS1 gene mutations, Fin-major and Fin-minor, both lead to an absence of nephrin and podocyte slit diaphragms, as well as a clinically severe form of NPHS1, the Finnish type of congenital nephrotic syndrome.

Topics: Blotting, Western; Finland; Gene Expression; Genes, Recessive; Genotype; Humans; Hypoproteinemia; In Situ Hybridization; Infant, Newborn; Kidney; Membrane Proteins; Microscopy, Electron; Mutation, Missense; Nephrotic Syndrome; Phosphoproteins; Proteins; Proteinuria; RNA, Messenger; Zonula Occludens-1 Protein