In Chinese children with steroid-resistant nephrotic syndrome (SRNS), it was reported that NPHS2 mutation was detected in 4.3%, which was lower than that in Caucasians (10-30%).
Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.
We generated podocin-deficient (Nphs2-/-) mice to investigate the function of podocin, a protein expressed at the insertion of the slit diaphragm in podocytes and defective in a subset of patients with steroid-resistant nephrotic syndrome and focal and segmental glomerulosclerosis.
Recessive podocin mutations were present in 18.1% (73 of 404) of families with SRNS, and 69.9% of these mutations were nonsense, frameshift, or homozygous R138Q.
Mutations in NPHS2, which encodes for podocin, an integral membrane protein of the glomerular epithelial cells (podocytes), represent a frequent cause of steroid-resistant nephrotic syndrome worldwide.
In steroid-resistant nephrotic syndrome (SRNS) Machuca et al. report that mutations of the recessive podocin gene cause adult-onset SRNS if the R229Q genetic variant occurs in a compound heterozygous state with another podocin mutation.
Knowledge of mutation rate of NPHS2 in different populations of SRNS patients facilitates the physician in planning a suitable genetic screening strategy for patients.
Recent studies have demonstrated that mutations in 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1, are associated with the pathogenesis of steroid-resistant nephrotic syndrome (SRNS).
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.
In vitro permeability activity (P(alb)) was determined in sera of five patients with autosomal recessive steroid-resistant nephrotic syndrome (NPHS2), an inherited condition indistinguishable from idiopathic FSGS on clinical grounds, but in which proteinuria is determined by homozygous mutations of podocin, a key component of the glomerular podocyte.