WT1 gene mutation c.1422delA resulting in Frasier syndrome

Abstract

Objective: Frasier syndrome (FS) is characterized by steroid resistant nephrotic syndrome and progressing renal disease because of focal and segmental glomerular sclerosis (FSGS) pending the end-stage renal failure (ESRF). Individual with a 46,XY karyotype have undermasculinized external genitalia and are at increased risk of gonadoblastoma. The syndrome is caused by the point mutation in the Wilms tumor gene (WT1) intron 9 splice donor site. The mutations responsible for FS are substitutions causing abnormal +KTS/-KTS isoforms ratio. We present a patient with the new type of the mutation which could be the reason of FS. Methods: An 8-year-old girl was suspected to have FS by clinical symptoms. Molecular genetic analysis was made to confirm the diagnosis. Results: The girl was referred to the Department of Pediatric Nephrology because of proteinuria, hypertension, pruritus and episodic vomiting for sixmonths. The clinical diagnosis of glomerulonephritis wasmade. Focal segmental glomerulosclerosis (FSGS) was detected after histological assessment of the renal biopsy. Prednisone treatment appeared to be ineffective and hemodialysis was started because of ESRF. The detailed anamnesis revealed the fact that the patient had the disorder of sexual differentiation (DSD) and suspected FS led to the analysis of the WT1 gene mutations. Clinical FS diagnosis was confirmed by the detection a c.1422delA mutation in 8 exon of WT1 gene. Conclusion: The new type of mutation c.1422delA in WT1 gene can be responsible for FS syndrome. WT1 gene expression analysis using quantitative PCR should be performed to confirm modifying +KTS/- KTS isoforms ratio.