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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References
Matsunaga, E. Hum. Genet. 57, 231–246 (1981).
Miller, R.W., Fraumeni, Jr., J.F. & Manning, M.D. New Engl. J. Med. 270, 922–927 (1964).
Denys, P., Malvaux, P., van den Berghe, H., Tanghe, W. & Proesmans., W. Arch. Fran. Ped. 24, 729–739 (1967).
Drash, A., Sherman, F., Hartmann, W.H. & Blizzard, R.M. J. Pediatr. 76, 585–593 (1970).
Call, K.M. et al. Cell 60, 509–520 (1990).
Gessler, M. et al. Nature 343, 774–778 (1990).
Haber, D.A. et al. Cell 61, 1257–1269 (1990).
Haber, D.A. et al. Proc. natn. Acad. Sci. U.S.A. 88, 9618–9622 (1991).
Rauscher III, F.J. et al. Science 250, 1259–1262 (1990).
Madden, S.L. et al. Science 253, 1550–1553 (1991).
Pritchard-Jones, K. et al. Nature 346, 194–197 (1990).
Pelletier, J. et al. Genes & Dev. 5, 1345–1356 (1991).
Pelletier, J. et al. Nature 353, 431–434 (1991).
Pelletier, J. et al. Cell 67, 437–447 (1991).
Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K. & Sekiya, T. Proc. natn. Acad. Sci. U.S.A. 86, 2766–2770 (1989).
Pavletich, N.P. & Pabo, C.O. Science 252, 809–817 (1991).
Lee, M.S., Gippert, G.P., Soman, K.V., Case, D.A. & Wright, P.E. Science 245, 635–637 (1989).
Miller, J., McLachlan, A.D. & Klug, A. EMBO J. 4, 1609–1614 (1985).
Vrana, K.E., Churchill, M.E.A., Tullius, T.D. & Brown, D.D. Molec. Cell. Biol. 8, 1684–1696 (1988).
Nardelli, J., Gibson, J., Vesque, C. & Charnay, P. Nature 349, 175–178 (1991).
Gibbs, R.A., Nguyen, P.-N., Edwards, A., Civitello, A.B. & Caskey, C.T. Genomics 7, 235–244 (1990).
Kazazian Jr, H.H. et al. EMBO J. 3, 593–596 (1984).
Treisman, R., Orkin, S.H. & Maniatis, T. Nature 302, 591–596 (1983).
Solnick, D. Nature 291, 508–510 (1981).
Parker, R. & Guthrie, C. Cell 41, 107–118 (1985).
Jacquier, A., Rodriguez, J.R. & Rosbash, M. Cell 43, 423–430 (1985).
Fouser, L.A. & Friesen, J.D. Cell 45, 81–93 (1986).
Séraphin, B. & Rosbash, M. Cell 63, 619–629 (1990).
Lapoumeroulie, C. et al. Nucl. Acids Res. 15, 8195–8204 (1987).
Zhuang, Y. & Weiner, A.M. Cell 46, 827–835 (1986).
Glade, P.R. & Beratis, N.G. Prog. med. Genet. 1, 1–48 (1976).
Langridge, J., Langridge, P. & Bergquist, P.L. Anal. Biochem. 103, 264–271 (1980).
McCoy, Jr., F.E., Franklin, W.A., Aronson, A.J. & Spargo, B.H. Am. J. surg. Path. 7, 387–395 (1983).
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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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DOI: https://doi.org/10.1038/ng0592-144
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