Document Detail


Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations.
MedLine Citation:
PMID:  19406966     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVES: 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.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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:
Gianluca Caridi; Maddalena Gigante; Pietro Ravani; Antonella Trivelli; Giancarlo Barbano; Francesco Scolari; Monica Dagnino; Luisa Murer; Corrado Murtas; Alberto Edefonti; Landino Allegri; Alessandro Amore; Rosanna Coppo; Francesco Emma; Tommaso De Palo; Rosa Penza; Loreto Gesualdo; Gian Marco Ghiggeri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-30
Journal Detail:
Title:  Clinical journal of the American Society of Nephrology : CJASN     Volume:  4     ISSN:  1555-905X     ISO Abbreviation:  Clin J Am Soc Nephrol     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-04     Completed Date:  2009-08-27     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  101271570     Medline TA:  Clin J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1065-72     Citation Subset:  IM    
Affiliation:
Division of Nephrology and Laboratory on Pathophysiology of Uremia Istituto Giannina Gaslini, Genova, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Child
Child, Preschool
Female
Follow-Up Studies
Genetic Variation
Heterozygote
Humans
Infant
Intracellular Signaling Peptides and Proteins / genetics*
Kaplan-Meier Estimate
Male
Membrane Proteins / genetics*
Nephrotic Syndrome / genetics*,  mortality*
Point Mutation
Chemical
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/NPHS2 protein; 0/nephrin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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