These data outline the clinical features of sporadic nephrotic syndrome due to podocin mutations (homozygous and heterozygous) in a representative population with broad phenotype, including patients with good response to drugs.
The present study has been performed to screen single nucleotide polymorphisms (SNPs) of the NPHS2 gene in a group of 90 Indian children suffering with NS (30 SSNS, 30 SRNS and 30 Controls) by PCR method followed by direct exon sequencing.
Data from large cohorts indicate that the risk of recurrence of nephrotic syndrome after renal transplantation in patients with podocin mutations is very low.
Looking at podocyte components conferring permselectivity properties to the kidney, we characterized the haplotype of podocin and found cosegregation of one specific allele in the two patients with nephrotic syndrome, suggesting a relationship between podocin features and proteinuria.
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.