Alteration in DNA-binding affinity of Wilms tumor 1 protein due to WT1 genetic variants associated with steroid - resistant nephrotic syndrome in children.

ABSTRACT: Approximately one third of children with steroid-resistant nephrotic syndrome (SRNS) carry pathogenic variants in one of the many associated genes. The WT1 gene coding for the WT1 transcription factor is among the most frequently affected genes. Cases from the Czech national SRNS database were sequenced for exons 8 and 9 of the WT1 gene. Eight distinct exonic WT1 variants in nine children were found. Three children presented with isolated SRNS, while the other six manifested with additional features. To analyze the impact of WT1 genetic variants, wild type and mutant WT1 proteins were prepared and the DNA-binding affinity of these proteins to the target EGR1 sequence was measured by microscale thermophoresis. Three WT1 mutants showed significantly decreased DNA-binding affinity (p.Arg439Pr

SUBMITTER: Bezdicka M 

PROVIDER: S-EPMC9130146 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature