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Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development

Nature Genetics volume 1, pages 144–148 (1992)Cite this article

Abstract

Denys–Drash syndrome is a rare human developmental disorder affecting the urogenital system and leading to renal failure, intersex disorders and Wilms' tumour. In this report, four individuals with this syndrome are described carrying germline point mutations in the Wilms' tumour suppressor gene, WT1. Three of these mutations were in the zinc finger domains of WT1. The fourth occurred within intron 9, preventing splicing at one of the alternatively chosen splice donor sites of exon 9 when assayed in vitro. These results provide genetic evidence for distinct functional roles of the WT1 isoforms in urogenital development.

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Authors and Affiliations

  1. Division of Pediatric Endocrinology, Children's Memorial Hospital, Chicago, Illinois, 60614, USA

    Wendy Bruening, Nabeel Bardeesy & Bernard L. Silverman

  2. Division of Nephrology, Children's Memorial Hospital, Chicago, Illinois, 60614, USA

    Richard A. Cohn

  3. Department of Pathology, University of Alberta, Edmonton, T6G 2R7, Canada

    Geoffrey A. Machin

  4. Department of Pediatrics, Wyler Children's Hospital, Chicago, Illinois, 60637, USA

    Andrew J. Aronson

  5. Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    David Housman

  6. Department of Experimental Medicine, McGill Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada

    Jerry Pelletier

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  1. Wendy Bruening
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  2. Nabeel Bardeesy
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Bruening, W., Bardeesy, N., Silverman, B. et al. Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development. Nat Genet 1, 144–148 (1992). https://doi.org/10.1038/ng0592-144

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