Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Cohen, Pinhas / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Feihong / Mericq, Veronica / Roth, Christian / Toppari, Jorma

Editorial Board Member: Battelino, Tadej / Buyukgebiz, Atilla / Cassorla, Fernando / Chrousos, George P. / Cutfield, Wayne / Fideleff, Hugo L. / Hershkovitz, Eli / Hiort, Olaf / LaFranchi, Stephen H. / Lanes M. D., Roberto / Mohn, Angelika / Root, Allen W. / Rosenfeld, Ron G. / Werther, George / Zadik, Zvi

12 Issues per year


IMPACT FACTOR 2016: 1.233

CiteScore 2016: 1.09

SCImago Journal Rank (SJR) 2016: 0.527
Source Normalized Impact per Paper (SNIP) 2016: 0.602

Online
ISSN
2191-0251
See all formats and pricing
More options …
Volume 27, Issue 1-2 (Jan 2014)

Issues

A novel insertion in the FOXL2 gene in a Chilean patient with blepharophimosis ptosis epicanthus inversus syndrome type I

Alejandro Martinez-Aguayo
  • Endocrinology Unit, Pediatric Division, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
  • These authors contributed equally to this work
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Helena Poggi
  • Molecular Biology Laboratory, Clinical Laboratory Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
  • These authors contributed equally to this work
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Andreina Cattani
  • Endocrinology Unit, Pediatric Division, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Marcela Molina
  • Endocrinology Unit, Pediatric Division, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Eliana Romeo
  • Molecular Biology Laboratory, Clinical Laboratory Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Marcela Lagos
  • Corresponding author
  • Laboratorio de Biología Molecular, Centro Médico San Joaquín, Vicuña Mackenna 4686, Macul, Santiago 6904413, Chile
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-09-13 | DOI: https://doi.org/10.1515/jpem-2013-0219

Abstract

Objective: A novel insertion in the forkhead transcription factor 2 (FOXL2) was identified in a Chilean patient with blepharophimosis, ptosis, and epicanthus inversus syndrome associated with premature ovarian failure (BPES type I). A clinical and molecular characterization of a patient with BPES type I was performed.

Method: We present a 16-year-old adolescent girl with surgically treated blepharophimosis, ptosis, and epicanthus inversus that was associated with delayed puberty and secondary amenorrhea at the age of 15, indicators that suggested that the patient had BPES type I. The FOXL2 gene was analyzed by sequencing its coding region.

Results: The sequence analysis of the FOXL2 gene revealed a novel heterozygous mutation: an 11 bp duplication (c.901_911dup11) that was predicted to encode a truncated protein (p.Pro305Argfs*54).

Conclusions: A novel out-of-frame duplication following the polyalanine domain in the FOXL2 gene was identified in a Chilean patient with BPES type I. This study characterized the molecular alterations in FOXL2 and confirmed the diagnosis, thereby providing information to allow for improved genetic counseling for the patient and her family.

Keywords: blepharophimosis; epicanthus inversus syndrome; forkhead transcription factor; premature ovarian failure; ptosis

References

  • 1.

    Cocquet J, Pailhoux E, Jaubert F, Servel N, Xia X, et al. Evolution and expression of FOXL2. J Med Genet 2002;39:916–21.CrossrefGoogle Scholar

  • 2.

    Hersmus R, Kalfa N, de Leeuw B, Stoop H, Oosterhuis JW, et al. FOXL2 and SOX9 as parameters of female and male gonadal differentiation in patients with various forms of disorders of sex development (DSD). J Pathol 2008;215:31–8.Web of ScienceGoogle Scholar

  • 3.

    Bentsi-Barnes IK, Kuo FT, Barlow GM, Pisarska MD. Human forkhead L2 represses key genes in granulosa cell differentiation including aromatase, P450scc, and cyclin D2. Fertil Steril 2010;94:353–6.Web of ScienceGoogle Scholar

  • 4.

    Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, et al. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat Genet 2001;27:159–66.CrossrefGoogle Scholar

  • 5.

    Ottolenghi C, Pelosi E, Tran J, Colombino M, Douglass E, et al. Loss of Wnt4 and Foxl2 leads to female-to-male sex reversal extending to germ cells. Hum Mol Genet 2007;16:2795–804.Web of ScienceCrossrefGoogle Scholar

  • 6.

    Jaubert F, Galmiche L, Lortat-Jacob S, Fournet JC, Fellous M. Foxl-2 in gonad development and pathology. Arkh Patol 2011;73:10–3.Google Scholar

  • 7.

    Verdin H, De Baere E. FOXL2 impairment in human disease. Horm Res Paediatr 2012;77:2–11.CrossrefPubMedGoogle Scholar

  • 8.

    Goswami D, Conway GS. Premature ovarian failure. Horm Res 2007;68:196–202.Web of ScienceCrossrefPubMedGoogle Scholar

  • 9.

    Harris SE, Chand AL, Winship IM, Gersak K, Aittomaki K, et al. Identification of novel mutations in FOXL2 associated with premature ovarian failure. Mol Hum Reprod 2002;8:729–33.CrossrefGoogle Scholar

  • 10.

    Bodega B, Porta C, Crosignani PG, Ginelli E, Marozzi A. Mutations in the coding region of the FOXL2 gene are not a major cause of idiopathic premature ovarian failure. Mol Hum Reprod 2004;10:555–7.CrossrefGoogle Scholar

  • 11.

    Gijsbers AC, D’Haene B, Hilhorst-Hofstee Y, Mannens M, Albrecht B, et al. Identification of copy number variants associated with BPES-like phenotypes. Hum Genet 2008;124:489–98.CrossrefPubMedGoogle Scholar

  • 12.

    Beysen D, De Jaegere S, Amor D, Bouchard P, Christin-Maitre S, et al. Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome. Hum Mutat 2008;29:E205–19.CrossrefGoogle Scholar

  • 13.

    den Dunnen JT, Antonarakis SE. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 2000;15:7–12.CrossrefGoogle Scholar

  • 14.

    Moumne L, Dipietromaria A, Batista F, Kocer A, Fellous M, et al. Differential aggregation and functional impairment induced by polyalanine expansions in FOXL2, a transcription factor involved in cranio-facial and ovarian development. Hum Mol Genet 2008;17:1010–9.Web of ScienceGoogle Scholar

  • 15.

    De Baere E, Beysen D, Oley C, Lorenz B, Cocquet J, et al. FOXL2 and BPES: mutational hotspots, phenotypic variability, and revision of the genotype-phenotype correlation. Am J Hum Genet 2003;72:478–87.PubMedCrossrefGoogle Scholar

  • 16.

    Fokstuen S, Antonarakis SE, Blouin JL. FOXL2-mutations in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES); challenges for genetic counseling in female patients. Am J Med Genet A 2003;117A:143–6.Google Scholar

  • 17.

    D’Haene B, Nevado J, Pugeat M, Pierquin G, Lowry RB, et al. FOXL2 copy number changes in the molecular pathogenesis of BPES: unique cohort of 17 deletions. Hum Mutat 2010;31:E1332–47.Web of ScienceGoogle Scholar

  • 18.

    Meduri G, Bachelot A, Duflos C, Bstandig B, Poirot C, et al. FOXL2 mutations lead to different ovarian phenotypes in BPES patients: case report. Hum Reprod 2010;25: 235–43.PubMedCrossrefGoogle Scholar

  • 19.

    Bell R, Murday VA, Patton MA, Jeffery S. Two families with blepharophimosis/ptosis/epicanthus inversus syndrome have mutations in the putative forkhead transcription factor FOXL2. Genet Test 2001;5:335–8.CrossrefGoogle Scholar

About the article

Corresponding author: Marcela Lagos, MD, Laboratorio de Biología Molecular, Centro Médico San Joaquín, Vicuña Mackenna 4686, Macul, Santiago 6904413, Chile, Phone: +56 2 235 48515, Fax: +56 2 235 48603, E-mail:


Received: 2013-05-31

Accepted: 2013-07-25

Published Online: 2013-09-13

Published in Print: 2014-01-01


Citation Information: Journal of Pediatric Endocrinology and Metabolism, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2013-0219.

Export Citation

©2014 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Hu Tan, Pu Yang, Haoxian Li, Qian Pan, Desheng Liang, and Lingqian Wu
Human Genome Variation, 2015, Volume 2, Page 15008

Comments (0)

Please log in or register to comment.
Log in