Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (84)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by De Baere, E.
Right arrow Articles by Messiaen, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by De Baere, E.
Right arrow Articles by Messiaen, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2001, Vol. 10, No. 15 1591-1600
© 2001 Oxford University Press

Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype–phenotype correlation

Elfride De Baere1,2, Michael J. Dixon3, Kent W. Small4, Ethylin W. Jabs5, Bart P. Leroy2, Koenraad Devriendt6, Yves Gillerot7, Geert Mortier1, Françoise Meire2, Lionel Van Maldergem7, Winnie Courtens8, Helle Hjalgrim9, Shangzhi Huang10, Inge Liebaers11, Nicole Van Regemorter12, Philippe Touraine13, Verayuth Praphanphoj5, Alain Verloes14, Nitin Udar4, Vivek Yellore4, Meenal Chalukya4, Svetlana Yelchits4, Anne De Paepe1, Frédérique Kuttenn13, Marc Fellous15, Reiner Veitia15 and Ludwine Messiaen1,+

1Department of Medical Genetics and 2Department of Ophthalmology, Ghent University Hospital, B-9000 Ghent, Belgium, 3School of Biological Sciences, Stopford Building, University of Manchester, Manchester, UK, 4The Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA, 5Institute of Genetic Medicine, Department of Pediatrics, Department of Medicine and Department of Plastic Surgery, The Johns Hopkins University School of Medicine, Baltimore, USA, 6Centre for Human Genetics, B-3000 Leuven, Belgium, 7Centre de Génétique Humaine, Institut de Pathologie et de Génétique, B-6280 Gerpinnes (Loverval), Belgium, 8Universitair Verplegingscentrum Brugmann-UKZKF, Brussels, Belgium, 9The John F. Kennedy Institute, Glostrup, Denmark, 10WHO Collaborating Center for Community Control of Inherited Diseases, Department of Medical Genetics, Peking Union Medical College, Beijing 100005, China, 11Department of Medical Genetics, University Hospital, Free University of Brussels, Belgium, 12Centre de Génétique, Hôpital Erasme, ULB, Brussels, Belgium, 13Department of Endocrinology and Reproductive Medicine, Hôpital Necker, Paris, France, 14Wallonia Center for Human Genetics, Liège University, Liège, Belgium and 15Immunogénétique Humaine, Institut Pasteur, Université Denis Didérot, Paris, France

Mutations in FOXL2, a forkhead transcription factor gene, have recently been shown to cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, a rare genetic disorder. In BPES type I a complex eyelid malformation is associated with premature ovarian failure (POF), whereas in BPES type II the eyelid defect occurs as an isolated entity. In this study, we describe the identification of novel mutations in the FOXL2 gene in BPES types I and II families, in sporadic BPES patients, and in BPES families where the type could not be established. In 67% of the patients studied, we identified a mutation in the FOXL2 gene. In total, 21 mutations (17 of which are novel) and one microdeletion were identified. Thirteen of these FOXL2 mutations are unique. In this study, we demonstrate that there is a genotype–phenotype correlation for either types of BPES by the finding that mutations predicted to result in a truncated protein either lacking or containing the forkhead domain lead to BPES type I. In contrast, duplications within or downstream of the forkhead domain, and a frameshift downstream of them, all predicted to result in an extended protein, cause BPES type II. In addition, in 30 unrelated patients with isolated POF no causal mutations were identified in FOXL2. Our study provides further evidence that FOXL2 haploinsufficiency may cause BPES types I and II by the effect of a null allele and a hypomorphic allele, respectively. Furthermore, we propose that in a fraction of the BPES patients the genetic defect does not reside within the coding region of the FOXL2 gene and may be caused by a position effect.

+ To whom correspondence should be addressed at: Department of Medical Genetics, Ghent University Hospital-OK5, De Pintelaan 185, B- 9000 Ghent, Belgium. Tel: +32 9 240 3603; Fax: +32 9 240 4970; Email: Ludwine.Messiaen@rug.ac.be


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
A. Dipietromaria, B. A. Benayoun, A.-L. Todeschini, I. Rivals, C. Bazin, and R. A. Veitia
Towards a functional classification of pathogenic FOXL2 mutations using transactivation reporter systems
Hum. Mol. Genet., September 1, 2009; 18(17): 3324 - 3333.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
S. P. Shah, M. Kobel, J. Senz, R. D. Morin, B. A. Clarke, K. C. Wiegand, G. Leung, A. Zayed, E. Mehl, S. E. Kalloger, et al.
Mutation of FOXL2 in Granulosa-Cell Tumors of the Ovary
N. Engl. J. Med., June 25, 2009; 360(26): 2719 - 2729.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. L. Blount, K. Schmidt, N. J. Justice, W. W. Vale, W. H. Fischer, and L. M. Bilezikjian
FoxL2 and Smad3 Coordinately Regulate Follistatin Gene Transcription
J. Biol. Chem., March 20, 2009; 284(12): 7631 - 7645.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
B. A. Benayoun, S. Caburet, A. Dipietromaria, M. Bailly-Bechet, F. Batista, M. Fellous, D. Vaiman, and R. A. Veitia
The identification and characterization of a FOXL2 response element provides insights into the pathogenesis of mutant alleles
Hum. Mol. Genet., October 15, 2008; 17(20): 3118 - 3127.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
D. Beysen, L. Moumne, R. Veitia, H. Peters, B. P. Leroy, A. De Paepe, and E. De Baere
Missense mutations in the forkhead domain of FOXL2 lead to subcellular mislocalization, protein aggregation and impaired transactivation
Hum. Mol. Genet., July 1, 2008; 17(13): 2030 - 2038.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
W. J. Watkins, S. E. Harris, M. J. Craven, A. L. Vincent, I. M. Winship, K. Gersak, and A. N. Shelling
An investigation into FOXE1 polyalanine tract length in premature ovarian failure
Mol. Hum. Reprod., March 1, 2006; 12(3): 145 - 149.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
A. Roy and M. M Matzuk
Deconstructing mammalian reproduction: using knockouts to define fertility pathways
Reproduction, February 1, 2006; 131(2): 207 - 219.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
O. Medina-Martinez, I. Brownell, F. Amaya-Manzanares, Q. Hu, R. R. Behringer, and M. Jamrich
Severe Defects in Proliferation and Differentiation of Lens Cells in Foxe3 Null Mice
Mol. Cell. Biol., October 15, 2005; 25(20): 8854 - 8863.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
L. E.L.M. Vissers, J. A. Veltman, A. G. van Kessel, and H. G. Brunner
Identification of disease genes by whole genome CGH arrays
Hum. Mol. Genet., October 15, 2005; 14(suppl_2): R215 - R223.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
K Raile, H Stobbe, R B Trobs, W Kiess, and R Pfaffle
A new heterozygous mutation of the FOXL2 gene is associated with a large ovarian cyst and ovarian dysfunction in an adolescent girl with blepharophimosis/ptosis/epicanthus inversus syndrome
Eur. J. Endocrinol., September 1, 2005; 153(3): 353 - 358.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
D. Goswami and G. S. Conway
Premature ovarian failure
Hum. Reprod. Update, July 1, 2005; 11(4): 391 - 410.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
D. Baron, J. Cocquet, X. Xia, M. Fellous, Y. Guiguen, and R. A Veitia
An evolutionary and functional analysis of FoxL2 in rainbow trout gonad differentiation
J. Mol. Endocrinol., December 1, 2004; 33(3): 705 - 715.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
S Caburet, A Demarez, L Moumne, M Fellous, E De Baere, and R A Veitia
A recurrent polyalanine expansion in the transcription factor FOXL2 induces extensive nuclear and cytoplasmic protein aggregation
J. Med. Genet., December 1, 2004; 41(12): 932 - 936.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
K. Gersak, S. E. Harris, W. J. Smale, and A. N. Shelling
A novel 30 bp deletion in the FOXL2 gene in a phenotypically normal woman with primary amenorrhoea: Case report
Hum. Reprod., December 1, 2004; 19(12): 2767 - 2770.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. Amiel, D. Trochet, M. Clement-Ziza, A. Munnich, and S. Lyonnet
Polyalanine expansions in human
Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R235 - R243.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. D. Pisarska, J. Bae, C. Klein, and A. J. W. Hsueh
Forkhead L2 Is Expressed in the Ovary and Represses the Promoter Activity of the Steroidogenic Acute Regulatory Gene
Endocrinology, July 1, 2004; 145(7): 3424 - 3433.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
W. Chang, C. Tilmann, K. Thoemke, F.-H. Markussen, L. D. Mathies, J. Kimble, and D. Zarkower
A forkhead protein controls sexual identity of the C. elegans male somatic gonad
Development, March 15, 2004; 131(6): 1425 - 1436.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
D. Schmidt, C. E. Ovitt, K. Anlag, S. Fehsenfeld, L. Gredsted, A.-C. Treier, and M. Treier
The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance
Development, February 15, 2004; 131(4): 933 - 942.
[Abstract] [Full Text] [PDF]

Home page
 Arch OphthalmolHome page
J. A. Smith, S. Vitale, G. F. Reed, S. A. Grieshaber, L. A. Goodman, V. H. Vanderhoof, K. A. Calis, and L. M. Nelson
Dry Eye Signs and Symptoms in Women With Premature Ovarian Failure
Arch Ophthalmol, February 1, 2004; 122(2): 151 - 156.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. A. Loffler, D. Zarkower, and P. Koopman
Etiology of Ovarian Failure in Blepharophimosis Ptosis Epicanthus Inversus Syndrome: FOXL2 Is a Conserved, Early-Acting Gene in Vertebrate Ovarian Development
Endocrinology, July 1, 2003; 144(7): 3237 - 3243.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
O. J. Lehmann, S. Tuft, G. Brice, R. Smith, A. Blixt, R. Bell, B. Johansson, T. Jordan, R. A. Hitchings, P. T. Khaw, et al.
Novel Anterior Segment Phenotypes Resulting from Forkhead Gene Alterations: Evidence for Cross-Species Conservation of Function
Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2627 - 2633.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
J Cocquet, E Pailhoux, F Jaubert, N Servel, X Xia, M Pannetier, E De Baere, L Messiaen, C Cotinot, M Fellous, et al.
Evolution and expression of FOXL2
J. Med. Genet., December 1, 2002; 39(12): 916 - 921.
[Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
S.E. Harris, A.L. Chand, I.M. Winship, K. Gersak, K. Aittomaki, and A.N. Shelling
Identification of novel mutations in FOXL2 associated with premature ovarian failure
Mol. Hum. Reprod., August 1, 2002; 8(8): 729 - 733.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
E De Baere, B Lemercier, S Christin-Maitre, D Durval, L Messiaen, M Fellous, and R Veitia
FOXL2 mutation screening in a large panel of POF patients and XX males
J. Med. Genet., August 1, 2002; 39(8): e43 - 43.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.