MO020: Rare mutation of the IQGAP1 protein in an Algerian family with corticosteroid-resistant nephrotic syndrome

Abstract BACKGROUND AND AIMS There is podocyte involvement in corticosteroid-resistant nephrotic syndrome. A certain number of proteins play an essential role in the biology of the podocyte; the mutation of these proteins generates the aforementioned pathology. The aim of this work is the determination of the rare mutation of the IQGAP1 protein, which is a protein involved in the remodeling of the actin cytoskeleton of the podocyte. METHOD We identified six patients in our family with corticosteroid-resistant nephrotic syndrome, including one death with four adults and two children from a consanguineous marriage with autosomal recessive transmission. It was noted that three deaths of unknown etiologies were reported at a very young age. RESULTS The patients had corticosteroid-resistant nephrotic syndrome. Nephrotic syndrome is discovered at the age of 4 years on average for two children and 20 years for four adults. Kidney biopsy showed minimal glomerular damage at 19%, mesangial proliferation at 6% and segmental and focal hyalinosis at 71%. The extra-renal manifestations observed were linked to complications of chronic renal failure. Alteration of the expression of IQGAP1 or of its cellular location, as well as structural or functional alterations of the protein could lead to abnormal interactions between the different complexes of the podocyte and the cytoskeleton; the specificity of the study is the discovery of an SNCRF in patients where they have only one mutation of the IQGAP1 gene without mutation of the other IQGAPs (2 and 3). CONCLUSION We have a very high consanguineous marriage rate, which explains why the transmission of recessive diseases is very important. The mutation of the IQGAP1 protein is inherited in an autosomal recessive fashion. A genetic investigation is essential. IQGAP1 can therefore be considered to be a factor influencing the progression of glomerulopathies. FIGURE 1: Genealogical tree. FIGURE 2: Study of the expression of the IQGAP1 protein.