title: A novel WT1 heterozygous nonsense mutation (p.K248X) causing a mild and slightly progressive nephropathy in a 46,XY patient with Denys-Drash syndrome.
abstract: WT1 mutations have been described in a variety of syndromes, including Denys-Drash syndrome (DDS), which is characterized by predisposition to Wilms' tumor, genital abnormalities and development of early nephropathy. The most frequent WT1 defects in DDS are missense mutations located in exons 8-9. Our aim is to report a novel WT1 mutation in a 46,XY patient with a DDS variant, who presented a mild nephropathy with a late onset diagnosed during adolescence. He had ambiguous genitalia at birth. At 4 months of age he underwent nephrectomy (Wilms' tumor) followed by chemotherapy. Ambiguous genitalia were corrected and bilateral gonadectomy was performed. Sequencing of WT1 identified a novel heterozygous mutation (c.742A>T) in exon 4 that generates a premature stop codon (p.K248X). Interestingly, this patient has an unusual DDS nephropathy progression, which reinforces that patients carrying WT1 mutations should have the renal function carefully monitored due to the possibility of late-onset nephropathy.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM42, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155, PAMB, 2º andar, Bloco 6, 05403-900 Sao Paulo, SP, Brazil.
authors.forename: Thatiana Evilen
authors.initials: TE
authors.lastname: da Silva
authors.forename: Mirian Yumie
authors.initials: MY
authors.lastname: Nishi
authors.forename: Elaine Maria Frade
authors.initials: EM
authors.lastname: Costa
authors.forename: Regina Matsunaga
authors.initials: RM
authors.lastname: Martin
authors.forename: Filomena Marino
authors.initials: FM
authors.lastname: Carvalho
authors.forename: Berenice Bilharinho
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Sorahia
authors.initials: S
authors.lastname: Domenice
mesh_terms: D001483:Base Sequence; D018389:Codon, Nonsense; D030321:Denys-Drash Syndrome / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D016162:Genes, Wilms Tumor; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000150:complications / Q000235:genetics*; D008297:Male; D025721:WT1 Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D025721:WT1 Proteins