title: Steroid-resistant nephrotic syndrome caused by novel WT1 mutation inherited from a mosaic parent.
abstract: 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.
authors.affiliation: a Molecular Medicine Center , Department of Medical Chemistry and Biochemistry, Medical University of Sofia , Sofia , Bulgaria ;
authors.forename: Olga
authors.initials: O
authors.lastname: Beltcheva
authors.affiliation: b SBAL Pediatric Diseases, Pediatric Nephrology and Hemodialysis Clinic, Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Anelia
authors.initials: A
authors.lastname: Boueva
authors.affiliation: a Molecular Medicine Center , Department of Medical Chemistry and Biochemistry, Medical University of Sofia , Sofia , Bulgaria ;
authors.forename: Reni
authors.initials: R
authors.lastname: Tzveova
authors.affiliation: b SBAL Pediatric Diseases, Pediatric Nephrology and Hemodialysis Clinic, Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Dimitar
authors.initials: D
authors.lastname: Roussinov
authors.affiliation: b SBAL Pediatric Diseases, Pediatric Nephrology and Hemodialysis Clinic, Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Marinova
authors.affiliation: a Molecular Medicine Center , Department of Medical Chemistry and Biochemistry, Medical University of Sofia , Sofia , Bulgaria ;
authors.forename: Radka
authors.initials: R
authors.lastname: Kaneva
authors.affiliation: a Molecular Medicine Center , Department of Medical Chemistry and Biochemistry, Medical University of Sofia , Sofia , Bulgaria ;
authors.forename: Vanio
authors.initials: V
authors.lastname: Mitev
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D016162:Genes, Wilms Tumor; D006801:Humans; D009030:Mosaicism; D020125:Mutation, Missense; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000305:Adrenal Cortex Hormones
keywords: Nephrotic syndrome; WT1; end-stage renal disease; mosaicism; proteinuria