FSGS cases expressed more uPAR than each of control and MCD (p = 0.0019; H = 12.57) and there was a positive and significant correlation between nephrin and podocin (p = 0.0026, rS = 0.6502) in these cases.
Among 42 patients, podocin was normally expressed in glomeruli in purpura nephritis, IgA nephropathy (IgAN), and minimal-change disease (MCD), while it was either decreased or absent in most subjects with focal segmental glomerulosclerosis (FSGS).
Identification of R229Q mutations may be of clinical importance, as NPHS2-associated disease appears to define a subgroup of FSGS patients unresponsive to corticosteroids.
This observation confirms the concept that recurrence of proteinuria may occur in inherited forms of FSGS so far reported only for patients carrying NPHS2 mutations and reinforces the idea on multifactorial origin of the disease.
NPHS2 mutations are responsible for autosomal recessive familial focal segmental glomerulosclerosis (FSGS), and these mutations were detected in both familial and sporadic forms of FSGS.
Familial and genetic forms of focal segmental glomerulosclerosis (FSGS) are associated with six different mutations in genes affecting the podocyte (NPHS2, ACTN4, CD2AP, WT1, TRPC6, and PLCE1).
The close temporal relationship of FSGS recurrence with CsA withdrawal and conversion to SRL suggests that caution should be exercised in the use of CsA-free immunosuppression also in patients with NPHS2-associated FSGS.
The interethnic differences in the occurrence of NPHS2 mutations may explain, in part, the previous observation that Arab patients with FSGS in Israel have a worse prognosis as compared with Jewish patients, despite similar presenting symptoms and medical management.
The most common mutations are in 4 genes, 3 of which are podocyte genes: NPHS1 (Finnish nephropathy), NPHS2 (podocin-induced focal segmental glomerulosclerosis), WT1 (diffuse mesangial sclerosis), and LAMB2 (Pierson syndrome).
We identified cases of FSGS that were unexpectedly diagnosed: In addition to mutations in the X-chromosomal <i>COL4A5</i> type IV collagen gene, nephrin and podocin polymorphisms aggravated kidney damage, leading to FSGS with ruptures of the basement membrane in a toddler and early renal failure in heterozygous girls.
Among 32 patients with two NPHS2 mutations who underwent kidney transplantation, only one developed late recurrence of focal segmental glomerulosclerosis (FSGS).
The results support the hypothesis that certain hypomorphic podocin variants may act as adverse genetic modifiers when co-inherited with COL4A3/A4 mutations, thus predisposing to FSGS and severe kidney function decline.
Abstract NPHS2 mutations are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis (FSGS), which is characterized by early childhood onset and rapid progression to chronic renal insufficiency.
A compound heterozygous podocin mutation was identified in our FSGS patient, leading to a truncated (podocin (V165X)) and a missense mutant protein (podocin (R168H)), respectively.
Our results suggest that the analysis of the NPHS2 gene mutation is not indicated as a routine diagnostic procedure in our population for adult-onset patients with FSGS.
Familial forms of focal segmental glomerulosclerosis (FSGS) are caused by mutations in genes at 1q25-31 (gene for steroid-resistant nephrotic syndrome 2 [NPHS2]), 11q21-22, 19q13 (gene for alpha-actinin 4 and NPHS1), and at additional unidentified chromosomal loci.
Results indicate possible clustering of causative NPHS2 mutations in FSGS-proven SRNS with onset before age one year old, and provide additional evidence that patients with childhood steroid-resistant nephrotic syndrome due to focal segmental glomerulosclerosis should first undergo analysis of NPHS2 coding sequence and WT1 exons 8 and 9 and surrounding exon/intron boundary sequences, followed by gender genotyping.
Large multicenter studies demonstrated that patients with two pathogenic NPHS2 mutations have a very low risk of recurring FSGS after renal transplantation, whereas patients with only one mutation presumably have a risk comparable to non-NPHS2FSGS patients.
NPHS2 mutations are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis (FSGS), which is characterized by early childhood onset (age less than 6 years) and rapid progression to chronic renal insufficiency.
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.