Human Genetics

, Volume 103, Issue 5, pp 547–556

Confirmation of FWT1 as a Wilms’ tumour susceptibility gene and phenotypic characteristics of Wilms’ tumour attributable to FWT1

  • N. Rahman
  • Fatima Abidi
  • Deborah Ford
  • Laura Arbour
  • Elizabeth Rapley
  • Patricia Tonin
  • David Barton
  • Gillian Batcup
  • J. Berry
  • Finbarr Cotter
  • Val Davison
  • Mary Gerrard
  • Elizabeth Gray
  • Richard Grundy
  • Magdi Hanafy
  • Derek King
  • Ian Lewis
  • Annette Ridolfi Luethy
  • Lisa Madlensky
  • Jill Mann
  • Anne O’Meara
  • Tony Oakhill
  • Mark Skolnick
  • Louise Strong
  • Dick Variend
  • Steven Narod
  • Charles Schwartz
  • Kathryn Pritchard-Jones
  • Michael R. Stratton
Original investigation

DOI: 10.1007/PL00008708

Cite this article as:
Rahman, N., Abidi, F., Ford, D. et al. Hum Genet (1998) 103: 547. doi:10.1007/PL00008708

Abstract

A susceptibility gene for Wilms’ tumour (WT), designated FWT1, was previously mapped to chromosome 17q12–q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • N. Rahman
    • 1
  • Fatima Abidi
    • 2
  • Deborah Ford
    • 3
  • Laura Arbour
    • 4
  • Elizabeth Rapley
    • 1
  • Patricia Tonin
    • 4
  • David Barton
    • 5
  • Gillian Batcup
    • 6
  • J. Berry
    • 7
  • Finbarr Cotter
    • 8
  • Val Davison
    • 9
  • Mary Gerrard
    • 10
  • Elizabeth Gray
    • 11
  • Richard Grundy
    • 8
  • Magdi Hanafy
    • 12
  • Derek King
    • 13
  • Ian Lewis
    • 14
  • Annette Ridolfi Luethy
    • 15
  • Lisa Madlensky
    • 16
  • Jill Mann
    • 17
  • Anne O’Meara
    • 5
  • Tony Oakhill
    • 7
  • Mark Skolnick
    • 18
  • Louise Strong
    • 19
  • Dick Variend
    • 10
  • Steven Narod
    • 20
  • Charles Schwartz
    • 2
  • Kathryn Pritchard-Jones
    • 21
  • Michael R. Stratton
    • 1
  1. 1.Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, UK e-mail: nazneen@icr.ac.uk, Tel.: +44-181-643-8901, Ext. 4661/4625, Fax: +44-181-643-0549GB
  2. 2.J.C. Self Research Institute for Human Genetics, Greenwood Genetic Center, Greenwood, S.C., USAUS
  3. 3.Section of Epidemiology, Institute of Cancer Research, Sutton, UKGB
  4. 4.Department of Human Genetics, McGill University, Montreal, CanadaCA
  5. 5.Our Lady’s Hospital for Sick Children, Dublin, IrelandIE
  6. 6.General Infirmary, Leeds, UKGB
  7. 7.Royal Hospital for Sick Children, Bristol, UKGB
  8. 8.Institute of Child Health, London, UKGB
  9. 9.West Midlands Regional Genetics Laboratory, Birmingham, UKGB
  10. 10.Sheffield Children’s Hospital, Sheffield, UKGB
  11. 11.Aberdeen Royal Infirmary, Aberdeen, UKGB
  12. 12.Stoke Mandeville Hospital, Aylesbury, UKGB
  13. 13.Royal Aberdeen Children’s Hospital, Aberdeen, UKGB
  14. 14.St. James Hospital, Leeds, UKGB
  15. 15.Inselspital, Berne, SwitzerlandCH
  16. 16.Mount Sinai Hospital, Toronto, CanadaCA
  17. 17.Birmingham Children’s Hospital, Birmingham, UKGB
  18. 18.Department of Medical Informatics, University of Utah, USAUS
  19. 19.Department of Pediatrics, University of Texas System Cancer Center, Houston, USAUS
  20. 20.Womens College Hospital, Toronto, CanadaCA
  21. 21.Section of Paediatrics, Institute of Cancer Research, Sutton, UKGB