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Functional evidence implicating FOXL2 in non syndromic premature ovarian failure and in the regulation of the transcription factor OSR2.
  1. Paul Laissue
  1. INSERM U567, Institut Cochin, Paris, France
    1. Besma Lakhal
    1. Department of Cytogenetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Tunisia
      1. Bérénice A Benayoun
      1. INSERM U567, Institut Cochin, Paris, France
        1. Aurélie Dipietromaria
        1. INSERM U567, Institut Cochin, Paris, France
          1. Rim Braham
          1. Department of Endocrinology, Farhat Hached University Teaching Hospital, Tunisia
            1. Hatem Elghezal
            1. Department of Cytogenetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Tunisia
              1. Pascal Philibert
              1. Hôpital Arnaud-de-Villeneuve and Service d'Hormonologie du Développement et de la Reproduction, France
                1. Ali Saâd
                1. Department of Cytogenetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Tunisia
                  1. Charles Sultan
                  1. Hôpital Arnaud-de-Villeneuve and Service d'Hormonologie du Développement et de la Reproduction, France
                    1. Marc Fellous
                    1. INSERM U567, Institut Cochin, Paris, France
                      1. Reiner Veitia (reiner.veitia{at}inserm.fr)
                      1. Institut Cochin. INSERM U567, CNRS UMR 8104/ENS, France

                        Abstract

                        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 localization 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 strongly activate 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 favor 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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