Addresses of the institutions:
Steroid resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) are a leading cause of end-stage renal disease (ESRD) in children, adolescents and adults. Recent progress in genetics allowed for the identification of causative genes in monogenic forms of SRNS. Although several SRNS genes could be identified mostly in younger children, the genetic basis of SRNS/FSGS in adolescents and adults is far from being understood. Especially adult patients have been undersupplied with genetic testing and only fragmented data on their genotypes are available. Reliable discrimination of genetic versus non-genetic forms is an imperative as the identification of monogenic FSGS has numerous implications in a precision medicine setting. Currently, the predominant application of short-read based sequencing techniques results in preferential detection of point mutations and small sized deletions/insertions while larger structural aberrations, gene rearrangements, and mutations in genomic repeats frequently escape detection. This project combines short-read based high capacity next generation sequencing (GPS/WES/WGS) with unparalleled structural variant analyses to overcome previous limitations in genetic analyses. The major goal of this project is to unravel the genetic basis of SRNS/FSGS and to define a pipeline for the molecular genetic analyses of SRNS/FSGS as a best-practice clinical routine at UoC.