title: Broad and unexpected phenotypic expression in Greek children with steroid-resistant nephrotic syndrome due to mutations in the Wilms' tumor 1 (WT1) gene.
abstract: Mutations in the Wilms' tumor suppressor gene 1 (WT1), most commonly within exons 8 or 9 or intron 9, are found in cases with the overlapping conditions of Denys-Drash and Frasier syndromes, as well as in patients with steroid-resistant nephrotic syndrome (SRNS). This study investigated the presence of WT1 gene mutations in cases with childhood SRNS, along with an evaluation of their clinical outcome. Twenty-seven Greek children with sporadic (19 cases) and familial (8 cases) SRNS were tested. Four phenotypically female patients with sporadic SRNS were found to carry de novo WT1 mutations, including two cases with p.R394W, and one case each with p.R366H, or n.1228+5G>A. Karyotype analysis found 46XX in three cases, but 46XY in one. No phenotype-genotype correlations were apparent in the WT1 gene positive cases since their clinical presentation varied broadly. Interestingly, one patient with a pathological WT1 nucleotide variation responded fully to combined therapy with cyclosporine A and corticosteroids. This study further illustrates that investigation of WT1 gene mutations is clinically useful to support definitive diagnosis in children presenting with SRNS in order to direct the most appropriate clinical management.
authors.affiliation: Medical Genetics, Athens University, "Aghia Sofia" Children's Hospital, Athens 115 27, Greece.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Megremis
authors.forename: Andromachi
authors.initials: A
authors.lastname: Mitsioni
authors.forename: Irene
authors.initials: I
authors.lastname: Fylaktou
authors.forename: Sofia Kitsiou
authors.initials: SK
authors.lastname: Tzeli
authors.forename: Filadelfia
authors.initials: F
authors.lastname: Komianou
authors.forename: Constantinos J
authors.initials: CJ
authors.lastname: Stefanidis
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kanavakis
authors.forename: Joanne
authors.initials: J
authors.lastname: Traeger-Synodinos
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006115:Greece / Q000453:epidemiology; D006801:Humans; D009154:Mutation; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D015995:Prevalence; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D025721:WT1 Proteins; D004247:DNA