title: Nephrin gene (NPHS1) in patients with minimal change nephrotic syndrome (MCNS).
abstract: BACKGROUND
  Minimal change nephrotic syndrome (MCNS) is a major problem in pediatric nephrology. While the pathogenesis of MCNS is not known, the latest discoveries in the genetic diseases indicate that glomerular epithelial cells (podocytes) and the slit diaphragm play a primary role in development of proteinuria. Because nephrin is known to be a major component of the slit diaphragm, we analyzed the structure of nephrin gene (NPHS1) in patients with MCNS of different severity.
  
  
  METHODS
  Clinical data and DNA samples were collected from 25 adults who had biopsy-proven MCNS in childhood. A direct sequencing was performed to all 29 exons of the NPHS1 gene. The significance of the findings was evaluated by similar analysis of DNA samples from 25 healthy control patients.
  
  
  RESULTS
  The analysis of NPHS1 revealed no specific MCNS-associated mutation. However, 5 of the 25 MCNS patients had heterozygous allelic variants leading to nonconservative amino acid substitutions not previously reported (G879R; R800C; T294I; A916S). One of the five patients also had the Fin-major mutation, and two had new, conservative amino acid substitutions (S786N; A342G). Three of the five patients were classified as steroid sensitive, one was an early nonresponder, and one patient showed clear resistance to steroid treatment. Six known polymorphic changes in NPHS1 were also found, three of them leading to amino acid changes. The number of allelic variants was high both in MCNS patients and control patients (mean 3.0 and 2.6).
  
  
  CONCLUSIONS
  The results suggest that genetic changes in nephrin may have a pathogenetic role in some patients with MCNS.
authors.affiliation: Hospital for Children and Adolescents and Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Anne-Tiina
authors.initials: AT
authors.lastname: Lahdenkari
authors.forename: Marjo
authors.initials: M
authors.lastname: Kestilä
authors.forename: Christer
authors.initials: C
authors.lastname: Holmberg
authors.forename: Olli
authors.initials: O
authors.lastname: Koskimies
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D009402:Nephrosis, Lipoid / Q000188:drug therapy / Q000235:genetics*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D013256:Steroids / Q000627:therapeutic use
chemical_list: D008565:Membrane Proteins; D011506:Proteins; D013256:Steroids; C113267:nephrin