Nephrotic Syndrome (NS) affects 16 in 100,000 children, making this condition one of the most common kidney diseases in childhood. The disease is usually classified as Congenital (CNS) when it manifests in utero or during the first three months of life, Infantile when the event occurs during the first year of life, in Childhood when symptoms occur between one year and 12 years and Juvenile, with onset between 12 and 18 years old. Approximately 20% of children with nephrotic syndrome are resistant to steroids and other immunosuppressors and are classified as Steroid Resistant (SRNS); the remaining 80% are Steroid Sensitive (SSNS). The main renal histology detected is focal segmental glomerulosclerosis (FSGS). The main cause of clinical manifestations is a dysfunction of the renal glomerular filtration barrier (GFB) leading to a massive loss of essential proteins in the urine. NS is a clinically and genetically heterogeneous disease with more than 20 genes already identified as being responsible for the etiology of a large proportion of SRNS cases. Our group has already screened the three main genes (NPHS2, NPHS1 and WT1) in 150 children using Sanger sequencing methodology. Mutations that correspond to the clinic symptoms were identified in only 9 patients (6%). The next step will be the establishment of Whole Exome Sequencing methodology to search for mutations in other genes to elucidate some cases that have still remained unclear. This project will bring further advances in the knowledge on the still incipient field of NS genetics in Brazil. We intend to implement and establish the high-throughput sequencing method starting with NS to gain skills in this methodology and then extend its application for the study of other important conditions in our laboratory.
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