Clinical Features and Long-Term Outcome of Nephrotic Syndrome Associated with Heterozygous NPHS1 and NPHS2 Mutations

Abstract

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 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.

Mutational analysis of podocyte genes in children with sporadic steroid-resistant nephrotic syndrome

“…Patient 7 was clinically diagnosed with NS at the age of 58 months; she failed to respond to either steroid or cyclosporin A treatment, and her renal pathology showed changes of FSGS. These clinical features were similar to those of patients with homozygous mutations or compound heterozygous mutations, or a heterozygous pathogenic mutation, in their NPHS1 genes, as reported previously (Heeringa et al, 2008;Philippe et al, 2008;Caridi et al, 2009;Santín et al, 2009). It is likely that the compound heterozygous state of the NPHS1 mutations caused development of SRNS in patient 7.…”

Study of Genetic Variation in Podocin Gene Associated with Idiopathic Nephrotic Syndrome

“…Several studies did not report any polymorphism in SRNS [18], however, higher percent of this polymorphism was found by many other studies [18]. In addition, The polymorphism R229Q was absent among SSNS and SRNS subcategories a finding which was detected by Landau et al [25] who did not find any polymorphisms in SSNS, as well as Lahdenkari et al, [26] and Caridi et al, [27]. Our results concerning the absence of the NPHS2 R229Q…”

Evidence that NPHS2-R229Q predisposes to proteinuria and renal failure in familial hematuria

“…It is now well established that R229Q is a frequent cause of nephrotic syndrome when found in compound heterozygosity with other NPHS2 mutations [11][12][13]. Additionally, Pereira et al [8] reported that R229Q is responsible for microalbuminuria in the general population.…”