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Mutational analysis of NPHS2 and WT1 genes in Saudi children with nephrotic syndrome.

Abdulla A Alharthi, Ahmed Gaber, Mohamed W AbuKhatwah, Abeer M Almalki, Abdullah A Muzallef, Mohamed M Hassan, Ehab I El-Hallous, Meshari M Dalbouh, Gadah H Ali, Hanan M Atyah

Background: Nephrotic syndrome is the predominant glomeurular disease in childhood. Mutations in numerous genes are known to be the reason for steroid-resistant nephrotic syndrome; however, the presence of these mutations seems to be effected by race sociocultural differences and interethnic group. Mutations in NPHS2 and WT1 genes record for nearly 20% and 5% of all children cases with steroid-resistant nephrotic syndrome, respectively. By contrast, mutations are absent from children with either steroid-dependent nephrotic syndrome or frequently-relapse nephrotic syndrome.

Methods: Mutation analysis was accomplished by direct sequencing of the complete 8 exons of NPHS2 and exons 8 and 9 of WT1 in 20 patients with steroid-resistant nephrotic syndrome, 25 with steroid-dependent nephrotic syndrome, and 13 with frequently-relapse nephrotic syndrome.

Results: Three pathogenic mutations in NPHS2 were detected within steroid-resistant nephrotic syndrome patients. One as a non-sense mutation in exon 1 that was reported previously, while the second was novel and found as missense mutation in exon 7. The third one was found in the NPHS2 promoter region. Additionally, for the first time, one pathogenic missense mutation in exon 8 of WT1 gene was found in one Saudi patient with steroid-resistant nephrotic syndrome. All four mutations were documented and submitted to the ClinVar database.

Conclusion: NPHS2 and WT1 genes mutations are risk factors for steroid-resistant nephrotic syndrome with about 15% and 5% in Saudi pediatric patients. More molecular studies are required to clarify other possibility genes that responsible for the development of steroidresistant nephrotic syndrome in Saudi children.