Genomic profiling in (recurrent) steroid-resistant nephrotic syndrome

• Applicants: Dr. Janine Altmüller; Privatdozent Dr. Bodo Beck
• Subject Area: Nephrology ; Human Genetics
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 418039699

The clinical and genetically heterogeneous spectrum of steroid resistant nephrotic syndrome and focal segmental glomerulosclerosis (SRNS/FSGS) constitutes a major cause of pediatric as well as adult onset endstage renal disease (ESRD) worldwide. Despite over 20 years of genetic studies in this field a substantial number of patients with ESRD (overall > 60% in children) are still left without a clear diagnosis. Especially adult patients have been underserved with genetic testing and only fragmented data on their genotypes exits. Renal replacement therapy (dialysis and kidney transplantation) is the only treatment option, but requires medical resources that are simply not available to most patients worldwide. A significant proportion of children and adults with FSGS (ca. 30%) experience recurrence of FSGS in the graft (FSGS-R). The pathophysiologic basis of FSGS-R remains still unclear. Since announcement of the KFO 329 and information on the SRNS/FSGS genomic profiling project (TP 8) went public we have received enormous positive feedback and have been able to recruit 45 additional FSGS patients and 11 patients with FSGS-R within a 2 months period. With the help of the new DFG sequencing call and the availability of the NovaSeq6000 platform at the CCG we would like to expand our project to 100 additional exomes of SRNS/FSGS cases and 90 genomes for singleton or trio analyses in FSGS-(R). Thereby, we want to meet the benevolent critique of the initial reviewers of the KFO that the gene hunting strategy could be more competitive by increasing the number of WGS and WGS/WES Trio analyses that have been limited in the original proposal for budget restrictions without compromising the thoroughness of the study.

• DFG Programme: Research Grants