Genetic alterations in the podocyte development and function are recognized in up to 29.5% of cases of steroid resistant nephrotic syndrome. In contrast, steroid sensitive nephrotic syndrome (SSINS) is thought to be an immune mediated disease, and specific genetic mutations have not yet been identified.
In order to detect a candidate gene for SSINS, we conducted an exome array in 2 healthy parents, a young non- affected sibling, and two non-identical twin brothers who have SSINS. Our preliminary results identified a candidate gene for the disease. Mutations were proven by Sanger validation test. Thereafter, in order to determine the effects of these mutations on the protein signaling pathway a blood-based flow cytometry assay was utilized. We investigated basal and post-stimulation activity of the protein by its phosphorylation status on specific tyrosine residues associated with activation and calcium+2 flux. We found a tendency of gain of function in the non-identical twins when compared to their parents.
In this study we found a tendency for a gain of function in a mutant protein that might play a role as a candidate gene in SSINS.
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