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Functional evidence implicating FOXL2 in non-syndromic premature ovarian failure and in the regulation of the transcription factor OSR2
  1. P Laissue1,2,3,
  2. B Lakhal4,
  3. B A Benayoun1,2,3,5,
  4. A Dipietromaria1,2,3,
  5. R Braham6,
  6. H Elghezal4,
  7. P Philibert7,8,
  8. A Saâd4,
  9. C Sultan7,8,
  10. M Fellous1,2,3,
  11. R A Veitia1,2,3,5
  1. 1
    INSERM U567, Institut Cochin, Paris, France
  2. 2
    CNRS, UMR 8104, Institut Cochin, Paris, France
  3. 3
    Université Paris Descartes, Paris, France
  4. 4
    Department of Cytogenetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia
  5. 5
    Université Paris Diderot, Paris, France
  6. 6
    Department of Endocrinology, Farhat Hached University Teaching Hospital, Sousse, Tunisia
  7. 7
    Unité d’Endocrinologie-Gynécologie Pédiatrique, Service de Pédiatrie, Hôpital Arnaud-de-Villeneuve and Service d’Hormonologie du Développement et de la Reproduction, Hôpital Lapeyronie, Centre Hospitalier Universitaire Montpellier, Montpellier, France
  8. 8
    Institut de Génétique Humaine, Centre Nationale de la Recherche Scientifique UPR1142, Montpellier, France
  1. Reiner A Veitia, reiner.veitia{at}


Background: FOXL2 encodes a forkhead transcription factor whose mutations are responsible for the blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), involving craniofacial/palpebral abnormalities often associated with premature ovarian failure (POF).

Results: We describe a FOXL2 variant (p.Gly187Asp) in a case of POF without BPES. The subcellular localisation of FOXL2-G187D was normal but its transactivation capacity tested on two reporter promoters, one of which should be relevant to the ovary, was significantly lower than that of normal FOXL2. However, FOXL2-G187D was able to activate strongly a reporter construct driven by the promoter of Osr2 (odd-skipped related 2 transcription factor), which we have suggested to be a crucial target of FOXL2 in the craniofacial region. This is compatible with the absence of BPES in our patient.

Conclusions: Our data provide evidence in favour of the implication of FOXL2 variants in non-syndromic POF and confirm the regulatory interaction between FOXL2 and OSR2 whose perturbation might contribute to the palpebral abnormalities observed in BPES patients.

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  • PL and BL contributed equally to this work

  • Funding: Our work is supported by the INSERM, the CNRS, the Université Paris-Diderot/Paris VII, the Fondation pour la Recherche Médicale (FRM), a project GIS-maladies rares and the Institut Universitaire de France (IUF).

  • Competing interests: None declared.

  • Patient consent: Obtained.