title: Genetic abnormalities and prognosis in patients with congenital and infantile nephrotic syndrome.
abstract: BACKGROUND
  Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) are caused primarily by mutations in genes that encode structural and regulatory proteins of the glomerular filtration barrier. The aim of this study was to determine genotype-phenotype correlations and prognosis in patients with CNS and INS.
  
  
  METHODS
  NPHS1, NPHS2, LAMB2 and the eighth and ninth exons of WT1 were sequenced in 80 and 22 patients with CNS and INS, respectively. Genotype-phenotype correlations and survival were evaluated.
  
  
  RESULTS
  Causative mutations were identified in 64.7 % of patients, of which NPHS1 mutations were the most common (37.4 %). The mutation detection rate was twofold higher in CNS patients than in INS patients (72.5 vs. 36.2 %). The most commonly mutated gene in CNS patients was NPHS1 (46.3 %) versus NPHS2 (13.6 %) and WT1 (13.6 %) in INS patients. NPHS2 mutations, female patients with NPHS1 mutations, and NPHS1 mutations affecting the transmembrane or intracellular domains of nephrin were associated with longer survival.
  
  
  CONCLUSIONS
  Based on our present findings, the likelihood of identification of a genetic cause decreases with increasing age at diagnosis. The underlying genetic abnormality should be identified as early as possible, as this knowledge will facilitate clinicians in their prognostic prediction and enable patients to receive appropriate genetic counseling.
authors.affiliation: Department of Pediatric Nephrology, Hacettepe University, Ankara, Turkey.
authors.forename: Onur
authors.initials: O
authors.lastname: Cil
authors.forename: Nesrin
authors.initials: N
authors.lastname: Besbas
authors.forename: Ali
authors.initials: A
authors.lastname: Duzova
authors.forename: Rezan
authors.initials: R
authors.lastname: Topaloglu
authors.forename: Amira
authors.initials: A
authors.lastname: Peco-Antić
authors.forename: Emine
authors.initials: E
authors.lastname: Korkmaz
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
mesh_terms: D017668:Age of Onset; D004252:DNA Mutational Analysis; D005260:Female; D016162:Genes, Wilms Tumor; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D007797:Laminin / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000401:mortality; D011379:Prognosis
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; D008565:Membrane Proteins; C407223:NPHS2 protein; C113267:nephrin; C058783:laminin beta2