title: Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations.
abstract: OBJECTIVE
  Mutations in nephrin (NPHS1) and podocin (NPHS2) genes represent a major cause of idiopathic nephrotic syndrome (NS) in children. It is not yet clear whether the presence of a single mutation acts as a modifier of the clinical course of NS.
  
  
  METHODS
  We reviewed the clinical features of 40 patients with NS associated with heterozygous mutations or variants in NPHS1 (n = 7) or NPHS2 (n = 33). Long-term renal survival probabilities were compared with those of a concurrent cohort with idiopathic NS.
  
  
  RESULTS
  Patients with a single mutation in NPHS1 received a diagnosis before those with potentially nongenetic NS and had a good response to therapies. Renal function was normal in all cases. For NPHS2, six patients had single heterozygous mutations, six had a p.P20L variant, and 21 had a p.R229Q variant. Age at diagnosis and the response to drugs were comparable in all NS subgroups. Overall, they had similar renal survival probabilities as non-NPHS1/NPHS2 cases (log-rank chi(2) 0.84, P = 0.656) that decreased in presence of resistance to therapy (P < 0.001) and in cases with renal lesions of glomerulosclerosis and IgM deposition (P < 0.001). Cox regression confirmed that the only significant predictor of dialysis was resistance to therapy.
  
  
  CONCLUSIONS
  Our data indicate that single mutation or variant in NPHS1 and NPHS2 does not modify the outcome of primary NS. These patients should be treated following consolidated schemes and have good chances for a good long-term outcome.
authors.affiliation: Division of Nephrology and Laboratory on Pathophysiology of Uremia Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Maddalena
authors.initials: M
authors.lastname: Gigante
authors.forename: Pietro
authors.initials: P
authors.lastname: Ravani
authors.forename: Antonella
authors.initials: A
authors.lastname: Trivelli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Barbano
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Monica
authors.initials: M
authors.lastname: Dagnino
authors.forename: Luisa
authors.initials: L
authors.lastname: Murer
authors.forename: Corrado
authors.initials: C
authors.lastname: Murtas
authors.forename: Alberto
authors.initials: A
authors.lastname: Edefonti
authors.forename: Landino
authors.initials: L
authors.lastname: Allegri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Amore
authors.forename: Rosanna
authors.initials: R
authors.lastname: Coppo
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
authors.forename: Tommaso
authors.initials: T
authors.lastname: De Palo
authors.forename: Rosa
authors.initials: R
authors.lastname: Penza
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000401:mortality*; D017354:Point Mutation
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; C113267:nephrin