SRNS-causing mutations of NPHS2 and WT1 were detected in 7 of 33 patients (21%), including those with nephrotic syndrome manifesting before one year old: five of seven patients.
[Characterization of the NPH2 gene, coding for the glomerular protein podocin, implicated in a familial form of cortico-resistant nephrotic syndrome transmitted as an autosomal recessive].
Our results allowed us to assign a disease locus (SRN1) to a defined chromosomal region on 1q25-1q31, thus confirming the existence of a distinct entity of autosomal recessive nephrosis.
Homozygous or compound heterozygous mutations in the podocin gene NPHS2 are found in 10-30% of pediatric cases of steroid resistant nephrosis and/or FSGS.
Nevertheless, the available data suggest that large epidemiological case-control studies to examine the association between NPHS2 variants and nephrotic syndrome are warranted.
In conclusion, nephrotic syndrome in children with truncating or homozygous R138Q mutations manifests predominantly before 6 yr of life, and the onset of disease is significantly earlier than for any other podocin mutations.
Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism.
Overall, data are here presented that underscore a major role of inherited defects of NPHS2 in NS in children (including a relevant impact in sporadic cases) and give the functional rationale for the association.
Gain-of-function mutations in the transient receptor potential (TRP) cation channel subfamily C member 6 (TRPC6) gene and mutations in the NPHS2 gene encoding podocin result in nephrotic syndromes.
Rare mutations in nephrosis 2 (NPHS2), encoding podocin, are found in patients with familial and sporadic steroid-resistant nephrotic syndrome and focal segmental glomerular sclerosis.
Patients carrying NPHS2 mutations and without a family history of nephrotic syndrome were indistinguishable from those with idiopathic FSGS on the basis of the clinical phenotype.
Of the 38 Hungarian patients screened, seven carried NPHS2 mutations on both alleles, of whom two-diagnosed with proteinuria through school screening programs at the age of 9.7 and 14 years, respectively-did not develop nephrotic syndrome in childhood.