A novel WT1 mutation in a 46,XY boy with congenital bilateral cryptorchidism, nystagmus and Wilms tumor
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A novel WT1 mutation in a 46,XY boy with congenital bilateral cryptorchidism, nystagmus and Wilms tumor Monica Terenziani & Michele Sardella & Beatrice Gamba & Maria Adele Testi & Filippo Spreafico & Gianluigi Ardissino & Fausto Fedeli & Franca Fossati-Bellani & Paolo Radice & Daniela Perotti
Received: 20 August 2008 / Revised: 14 October 2008 / Accepted: 23 October 2008 / Published online: 2 December 2008 # IPNA 2008
Abstract The WT1 gene plays a crucial role in urogenital and gonadal development. Germline WT1 alterations have been described in a wide spectrum of pathological conditions, including kidney diseases, genital abnormalities and Wilms tumor (WT), frequently occurring in combination. We report on a novel WT1 nonsense mutation (c.1105C>T), introducing a premature stop codon in exon
M. Terenziani : F. Spreafico : F. Fossati-Bellani Department of Medical Oncology, Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy M. Sardella : B. Gamba : P. Radice : D. Perotti (*) Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milan, Italy e-mail: [email protected] M. A. Testi Unit of Anatomic Pathology B, Department of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy G. Ardissino Unit of Pediatric Nephrology, Dialysis and Transplantation, Department of Pediatrics, IRCCS Fondazione Ospedale Maggiore Policlinico-Mangiagalli, Milan, Italy F. Fedeli Department of Pediatrics, Ospedale Niguarda Cà Granda, Milan, Italy P. Radice F.I.R.C. Institute of Molecular Oncology Foundation, Milan, Italy
8 (p.Q369X), in a young XY male patient who presented with bilateral cryptorchidism, nystagmus, mild proteinuria and WT, but no sign of severe nephropathy. Although the majority of congenital urogenital abnormalities are not due to constitutional defects of the WT1 gene, our findings provide a rational for considering WT1 mutational analysis as one of the screening options in newborns with congenital defects of the urogenital tract due to the associated high risk of WT. Keywords Cryptorchidism . Proteinuria . Truncating mutation . Wilms tumor . WT1
Introduction The Wilms tumor (WT) suppressor gene WT1, mapped to chromosome 11p13, encodes a zinc-finger transcription factor required for the normal development and functioning of the urogenital tract [1]. WT1 consists of ten exons, with two alternative splicings involving the 17 amino acids coded by exon 5 and the KTS residues coded by the last nine nucleotides of exon 9, thus generating four different mRNA isoforms [2]. Exons 1–6 are involved in transcriptional regulation and protein homodimerization, while exons 7–10 encode the four zinc-fingers of the DNAbinding domains [3, 4]. Constitutional WT1 gene alterations are involved in a wide spectrum of pathologies, including syndromes and malignancies. Phenotype–genotype correlations have been established, but exceptions have been observed. Chromo
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