Nphs2 Mutations in Familial Steroid Resistant Nephrotic Syndrome in Gaza

Background: Nephrotic syndrome (NS) is characterized by edema, massive proteinuria, hypoalbuminemia, hyperlipidemia, and may progress to end stage renal disease. Based on the response to steroid therapy, NS is categorized as steroid-sensitive or steroid-resistant (SRNS). SRNS is inherited as an autosomal recessive disorder with NPHS2 being the most frequently mutated gene. NPHS2 encodes the glomerular protein podocin, which has an important role in controlling slit membrane permeability and glomerular ultrafiltration. Objective: The spectrum and frequency of NPHS2 mutations in Palestine have not been explored before. The aim of this study is to identify NPHS2 pathogenic mutations associated with SRNS in Palestinian families. Methods: Twenty SRNS-diagnosed patients were recruited from The Rantisi Children Hospital of Gaza. All the eight exons of the NPHS2 gene were PCR-amplified from patients genomic DNAs using primers located on the intron-exon boundaries. Direct sequencing of the purified PCR fragments was then ensued by automated Sanger sequencing method. Nucleotide changes were verified by comparing obtained sequences with the reference gene sequence stored in the NCBI database. Results: Analysis of the obtained sequences identified previously known mutations in 3 (15%) of the patients. Two of the mutations, p. G130K and p. R229Q were missense mutations and the third, p. R138X was a nonsense mutation. All mutations were present in homozygous form. Conclusions: The current study reports the identification of p. G130K, p. R138X, and p. R229Q NPHS2 mutations in SRNS patients in Gaza