Dataset Information

Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations.

ABSTRACT:

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.

SUBMITTER: Caridi G

PROVIDER: S-EPMC2689885 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Publications

Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations.

Caridi Gianluca G Gigante Maddalena M Ravani Pietro P Trivelli Antonella A Barbano Giancarlo G Scolari Francesco F Dagnino Monica M Murer Luisa L Murtas Corrado C Edefonti Alberto A Allegri Landino L Amore Alessandro A Coppo Rosanna R Emma Francesco F De Palo Tommaso T Penza Rosa R Gesualdo Loreto L Ghiggeri Gian Marco GM

Clinical journal of the American Society of Nephrology : CJASN 20090430 6

<h4>Background and objectives</h4>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.<h4>Design, setting, participants, & measurements</h4>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 pro ...[more]

PMID: 19406966

Similar Datasets

Project description:BackgroundNephrotic syndrome is traditionally classified on the basis of the response to standard steroid treatment. Mutations in more than 24 genes have been associated with nephrotic syndrome in children, although the great majority of steroid-resistant cases have been attributed to mutations in three main genes: NPHS1, NPHS2 and WT1. The aims of this study were to identify mutations in these genes more frequently reported as mutated and to characterize each variation using different in silico prediction algorithms in order to understand their biological functions.MethodsWe performed direct sequence analysis of exons 8 and 9 of WT1, 8 exons of NPHS2 and 29 exons of NPHS1, including NPHS2 and NPHS1 intron-exon boundary sequences, as well as 700 bp of the 5' UTR from both genes in 27 steroid-resistant patients aged between 3 months and 18 years.ResultsAnalysis of the NPHS2 gene revealed four missense mutations, one frameshift mutation and three variations in the 5' UTR. Four patients presented compound heterozygosis, and four other patients presented one heterozygous alteration only. WT1 and NPHS1 gene analysis did not reveal any mutations.DiscussionThis is the first study focusing on genetics of SRNS in Brazilian children. Identification of mutations is important because it could influence physicians' decision on patient treatment, as patients carrying mutations can be spared the side effects of immunosuppressive therapy and ultimately could be considered for kidney transplantation from a living donor.ConclusionsAfter molecular analysis of the genes more frequently reported as mutated in 27 steroid-resistant nephrotic syndrome patients, we identified NPHS2 mutations confirming the hereditary character of the kidney disease in only 14.8% of patients. Therefore, the next step is to perform a next generation sequencing based analysis of glomeluropathy-related panel of genes for the remaining patients in order to search for mutations in other genes related to steroid-resistant nephrotic syndrome.

Dataset Information

Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Publications

Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations.

Similar Datasets

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