A female infant with Frasier syndrome showing splice site mutation in Wilms' tumor gene (WT1) intron 9.

摘要

Wilms' tumor gene (WT1) abnormality leads to various disorders of differentiation as well as renal and urinary system abnormalities. Here we present a case of WT1 abnormality and steroid-resistant nephrotic syndrome in a female infant. The 3-year-old patient was initially diagnosed with proteinuria at an annual mass screening program for children aged three years and was referred to our hospital. She met the diagnostic criteria for nephrotic syndrome and showed normal renal function. The patient was treated with corticosteroids; however her condition showed resistance to corticosteroids. On renal biopsy, she was diagnosed with focal segmental glomerulosclerosis (FSGS). Because of the possibility of WT1 abnormality, an exon array analysis was conducted, which ruled out Denys-Drash Syndrome (DDS). The patient was then diagnosed with Frasier Syndrome (FS) on the basis of donor site mutation (IVS9+5G > A) of the splice site in the intron 9. Reports of female infants with FS are extremely rare. FS is one of the pre-mRNA splicing diseases, in which the occurrence of symptoms is associated with a decrease in the ratio of the lysine-threonine-serine (+/- KTS) isoform of the WT1 protein. A typical case exhibits 46 XY male karyotype and is characterized by male pseudohermaphroditism with cord-like gonadal structures as well as progressive nephropathy caused by FSGS. However, in female infants without such extrarenal signs, it is necessary to consider the analysis for WT1 intron 9 for conclusive diagnosis of FS, because the presence of nephropathy is the only symptom for possible detection.