Slow progressive FSGS associated with an F392L WT1 mutation.
Constitutional missense mutations in the WT1 gene are usually associated with the Denys-Drash syndrome, characterized by a rapid progressive nephropathy, male pseudohermaphroditism, and an increased risk for Wilms tumor. We report here a patient with scrotal hypospadias and a slow progressive nephropathy due to focal and segmental glomerulosclerosis. WT1 mutation analysis revealed a constitutional missense mutation in exon 9 resulting in an exchange F392L. This mutation has previously been reported by others in a patient with a similar mild course of nephropathy. In contrast, a mutation in the corresponding codon of exon 8 (F364L) was previously found by us in a patient with a very rapid progression to end-stage renal disease. Whether the position of a mutation may influence the course of the nephropathy must be evaluated in a larger patient cohort. The individual tumor risk for this alteration cannot be given at present because neither of the two patients has shown evidence of a Wilms tumor or a gonadoblastoma to date.
Kaltenis
Petras
P
Vilnius University Children's Hospital, Vilnius, Lithuania.
Schumacher
Valérie
V
Jankauskiene
Augustina
A
Laurinavicius
Arvydas
A
Royer-Pokora
Brigitte
B
D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D030321:Denys-Drash Syndrome / Q000235:genetics* / Q000503:physiopathology*; D018450:Disease Progression; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D025721:WT1 Proteins / Q000737:chemistry / Q000235:genetics*
D025721:WT1 Proteins