title: Truncating Wilms Tumor Suppressor Gene 1 Mutation in an XX Female with Adult-Onset Focal Segmental Glomerulosclerosis and Streak Ovaries: A Case Report.
abstract: About 30% of children with nephrotic syndrome (NS) have inherited forms. Among them, mutations in Wilms tumor suppressor gene 1 (WT1) are a well characterized cause associated with steroid-resistant NS, Wilms tumor, and urogenital malformation in males. However, the role of WT1 mutations in adult-onset focal segmental glomerulosclerosis (FSGS) is unclear. We report the case of a 38-year-old female with FSGS. She had been diagnosed with streak ovaries during diagnostic workup for infertility. Mutational analysis identified the heterozygous mutation c.1372C>T (p.Arg458*) in WT1 and the heterozygous non-neutral polymorphism c.868G>A (p.Arg229Gln) in NPHS2. Chromosomal analysis revealed a normal 46,XX female karyotype. Our case highlights that WT1 mutations should be considered in XX females with adult-onset FSGS, especially if urogenital abnormalities are present.
authors.affiliation: Institute of Human Genetics, Technical University Munich, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoefele
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Kemper
authors.forename: Ulf
authors.initials: U
authors.lastname: Schoenermarck
authors.forename: Susanna
authors.initials: S
authors.lastname: Mueller
authors.forename: Hanns-Georg
authors.initials: HG
authors.lastname: Klein
authors.forename: Anja
authors.initials: A
authors.lastname: Lemke
mesh_terms: D000328:Adult; D017668:Age of Onset; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D016162:Genes, Wilms Tumor; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007247:Infertility, Female / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D010053:Ovary / Q000002:abnormalities*; D020641:Polymorphism, Single Nucleotide
chemical_list: D018389:Codon, Nonsense; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein