Steroid-resistant nephrotic syndrome (SRNS) is a severe childhood disorder frequently progressing toward renal failure. Among its genetic causes are mutations in the Wilms tumor gene, WT1, which codes for a transcription factor with key role for the embryonic development of the genitourinary tract as well as for maintaining podocyte differentiation and slit diaphragm structure in adults. Defects in WT1 are associated with sporadic cases of both syndromic and isolated SRNS. We report here a novel WT1 mutation associated with SRNS in a female patient, which leads to a Cys428Ser substitution on protein level, affecting one of the cysteine residues responsible for zinc binding in the second zinc finger domain. Surprisingly, the mutation identified in the patient was found to be inherited from the healthy mosaic mother. The presence of mosaicism was confirmed using quantitative polymerase chain reaction (PCR) high-resolution melting. The clinical implications of this finding for the family are discussed.
Keywords: Nephrotic syndrome; WT1; end-stage renal disease; mosaicism; proteinuria.