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Identification of 34 novel and 56 known FOXL2 mutations in patients with blepharophimosis syndrome†

  1. Diane Beysen1,
  2. Sarah De Jaegere1,
  3. David Amor2,
  4. Philippe Bouchard3,
  5. Sophie Christin-Maitre3,
  6. Marc Fellous4,
  7. Philippe Touraine5,
  8. Arthur W. Grix6,
  9. Raoul Hennekam7,
  10. Françoise Meire8,9,
  11. Nina Oyen10,
  12. Louise C. Wilson11,
  13. Dalit Barel12,
  14. Jill Clayton-Smith13,
  15. Thomy de Ravel14,
  16. Christian Decock8,
  17. Patricia Delbeke8,
  18. Regina Ensenauer15,
  19. Friedrich Ebinger16,
  20. Gabriele Gillessen-Kaesbach17,
  21. Yvonne Hendriks18,
  22. Virginia Kimonis19,
  23. Rachel Laframboise20,
  24. Paul Laissue4,
  25. Kathleen Leppig21,
  26. Bart P. Leroy1,8,
  27. David T. Miller22,
  28. David Mowat23,
  29. Luitgard Neumann24,
  30. Astrid Plomp25,
  31. Nicole Van Regemorter26,
  32. Dagmar Wieczorek17,
  33. Reiner A. Veitia4,
  34. Anne De Paepe1,
  35. Elfride De Baere1,*

Article first published online: 18 JUL 2008

DOI: 10.1002/humu.20819

Issue

Human Mutation

Human Mutation

Special Issue: Special Issue: Assessing Mutation Pathogenicity in Cancer Susceptibility Genes

Volume 29, Issue 11, pages E205–E219, November 2008

Additional Information

How to Cite

Beysen, D., De Jaegere, S., Amor, D., Bouchard, P., Christin-Maitre, S., Fellous, M., Touraine, P., Grix, A. W., Hennekam, R., Meire, F., Oyen, N., Wilson, L. C., Barel, D., Clayton-Smith, J., de Ravel, T., Decock, C., Delbeke, P., Ensenauer, R., Ebinger, F., Gillessen-Kaesbach, G., Hendriks, Y., Kimonis, V., Laframboise, R., Laissue, P., Leppig, K., Leroy, B. P., Miller, D. T., Mowat, D., Neumann, L., Plomp, A., Van Regemorter, N., Wieczorek, D., Veitia, R. A., De Paepe, A. and De Baere, E. (2008), Identification of 34 novel and 56 known FOXL2 mutations in patients with blepharophimosis syndrome. Human Mutation, 29: E205–E219. doi: 10.1002/humu.20819

Author Information

  1. 1

    Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium

  2. 2

    Genetic Health Services Victoria, Royal Children's Hospital, Parkville, Australia

  3. 3

    Service d'Endocrinologie, Hôpital Saint-Antoine, Paris, France

  4. 4

    INSERM U709 Génomique et Epigénétique des Pathologies Placentaires and Universités Paris V & VII, Paris, France

  5. 5

    Department of Endocrinology and Reproductive Medicine, Pitie-Salpetrière Hospital, Paris, France

  6. 6

    The Permanente Medical Group, Department of Medical Genetics, Sacramento, California, USA

  7. 7

    Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

  8. 8

    Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium

  9. 9

    Ophthalmology Department, HUDERF-ULB, Brussels, Belgium

  10. 10

    Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

  11. 11

    Clinical and Molecular Genetics Unit, Institute of Child Health and Great Ormond Street Hospital, London, UK

  12. 12

    The Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

  13. 13

    Academic Department of Medical Genetics, St. Mary's Hospital, Manchester, United Kingdom

  14. 14

    Center for Human Genetics, Catholic University of Leuven, Belgium

  15. 15

    Departments of Laboratory Medicine & Pathology and Medical Genetics, Mayo Clinic College of Medicine, Rochester, USA

  16. 16

    Department of Pediatric Neurology, University Children's Hospital, Heidelberg, Germany

  17. 17

    Universitätsklinikum Essen, Institut für Humangenetik, Essen, Germany

  18. 18

    Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

  19. 19

    Department of Pediatrics, University of California, Irvine, Orange, California, USA

  20. 20

    Clinical Genetics Division, Department of Paediatrics and Medicine, CHUL, CHUQ, Faculty of Medicine, Laval University, Quebec, Canada

  21. 21

    Genetic Services, Group Health Cooperative (K.A.L.), Seattle, USA

  22. 22

    Division of Genetics, Children's Hospital, Boston, USA

  23. 23

    Sydney Children's Hospital, Dept of Clinical Genetics, Randwick, Australia

  24. 24

    Humangenetik, Charite Campus Virchow, Berlin, Germany

  25. 25

    Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands

  26. 26

    Medical Genetics Department, Hôpital Erasme-ULB, Brussels, Belgium

*Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium

  1. †

    Communicated by David L. Rimoin

Publication History

  1. Issue published online: 24 OCT 2008
  2. Article first published online: 18 JUL 2008
  3. Manuscript Accepted: 28 MAR 2008
  4. Manuscript Received: 16 OCT 2007

Funded by

  • grant BOF2002/ DRMAN/047 from the Bijzonder Onderzoeksfonds from Ghent University (to D.B.)
  • grant 1.5.244.05 from the Research Foundation - Flanders (FWO-Vlaanderen) (to E.D.B.)

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Keywords:

  • BPES;
  • FOXL2;
  • phenotype;
  • genotype-phenotype correlations

Abstract

Blepharophimosis syndrome (BPES) is caused by loss-of-function mutations in the single-exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in-frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype-phenotype correlations, emphasizing the need to interpret genotype-phenotype correlations individually and always in the context of further clinical observations. © 2008 Wiley-Liss, Inc.

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