Detection and functional characterization of genetic mutations in familial and sporadic focal segmental glomerulosclerosis

Abstract

Introduction: Focal segmental glomerulosclerosis (FSGS) and the steroid-resistant nephrotic syndrome (SRNS) in childhood can be caused by mutations in the genes encoding proteins that are essential for normal podocyte structure and/or function.Objectives: Search of mutations in familial FSGS and/or SRNS with onset in childhood in Brazilian patients; evaluation of pathogenicity of novel mutations by functional studies; implantation of the methodology in our service, as it would allow the clinical application in this and other familial glomerulopathies; definition of genotype-phenotype correlation for the mutations identified and and of the situations in which the genetic analysis would be indicated.Methods: Patients (and consanguineous relatives) with familial FSGS and/or children with SRNS will be included. The analysis of the genetic material will be performed by the exome technique and, if any changes are found, Sanger sequencing will be performed. The functional studies of the novel mutations it will be done by in silico analysis, podocyte characterization and/or gene expression analysis.Justificative: The study of mutations in this group of patients is necessary and not easily accessible in Brazil. Our service is reference in familial glomerulopathies and proper genetic evaluation may contribute to increase knowledge on such diseases and to improve healthcare of patients and their families. Genetic testing may be used to define prognosis, reproductive counseling, selection of appropriate therapies, and screening for donor eligibility among family members in kidney transplantation. (AU)