Childhood Nephrotic Syndrome Response to Steroid Therapy and the Relationship to Nphs2 Gene Mutation: a Multicenter Study in Saudi Arabia

Background: Nephrotic syndrome (NS) is an expression of many glomerular diseases and not a disease in itself. Based on response to steroids, NS is categorized into steroid-sensitive nephrotic syndrome (SSNS) or steroid-resistant nephrotic syndrome (SRNS). SRNS patients are at a high risk of developing end-stage renal disease. The aim of the study was to evaluate steroid response and the prevalence of NPHS2 gene mutations in Saudi children with NS. Mutations in the NPHS2 podocin gene on chromosome 1 are the cause of a familial, autosomal recessive SRNS with the most frequently reported variant R229Q. Materials & Methods: The study involved 74 Saudi children with NS, selected (by pediatric nephrology consultants) in 2014 from the pediatric nephrology clinics of different hospitals across regions in Saudi Arabia. Intravenous blood samples were drawn in sterile tubes containing ethylenediaminetetraacetic acid (EDTA). Genomic DNA samples were isolated and PCR products were assessed by restriction enzyme digestion to identify R229Q and R291W mutations. Positive results derived from DNA capillary sequencing analysis confirmed R229Q mutation. Results: Of the 74 children, 34.3% had SRNS. Of these, only 27% had a positive family history of this condition. Within the NPHS2 gene, we found one R229Q missense mutant allele. R291W mutation was absent. Conclusion: We identified an R229Q mutation in a lower frequency compared with other ethnic populations. However, one has to screen more genetic loci within the NPHS2 gene. Other responsible genes, for example, NPHS1, NPHS3, WT1, and ACTN4, could be investigated for this purpose.