Pawel Dubiela

Background: Although steroid therapy is a standard of care for nephrotic syndrome treatment, 15–20% of patients do not respond to it. Finding the genetic background is possible in >10% of steroid-resistant nephrotic syndrome (SRNS) cases. Variants in genes encoding nuclear pore complex proteins are a novel cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent studies suggest NUP93 variants to be a significant cause of paediatric onset SRNS. The clinical data on certain variants and disease history are still very limited. Methods and results: We report the SRNS case of a 12-year-old boy with two detected NUP93 variants, which are pathogenic and possibly pathogenic. The onset of the disease was early and severe. The patient was admitted to the paediatric nephrology department due to nephrotic-range proteinuria and hypoalbuminemia with a long medical history of steroid and non-steroid immunosuppressive treatment. The genetic panel targeting 50 genes, clinically relevant for nephrotic syndrome, was performed. The only gene which was found to be affected by mutations, namely c.2326C>T and c.1162C>T, respectively, was NUP93. Conclusions: NUP93 variants are rarely identified as causes of SRNS. Clinical data are of utmost importance to establish the standard of care for SRNS patients suffering from this genetic disfunction. This is the first case of a heterozygous patient with the c.2326C>T and c.1162C>T variants and confirmed clinical history of the SRNS described so far. Our data suggest the clinical relevance of the c.1162C>T variant.