Journal of Human Genetics and Genomics

Published by: Kowsar

Molecular Genetic Analysis of FOXL2 Gene in Two Iranian Families with Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome

Nooshin Asgari 1 , Mohammad Taghi Akbari 1 , 2 , * , Faravareh Khordadpoor Deilamani 1 and Gholamreza Babamohammadi 1
Authors Information
1 Tehran Medical Genetics Laboratory, Tehran, IR Iran
2 Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IR Iran
Article information
  • Journal of Human Genetics and Genomics: April 2017, 1 (1); e64100
  • Published Online: April 25, 2017
  • Article Type: Research Article
  • Received: February 15, 2017
  • Revised: March 3, 2017
  • Accepted: April 9, 2017
  • DOI: 10.5812/jhgg.64100

How to Cite: Asgari N, Akbari M T, Khordadpoor Deilamani F, Babamohammadi G. Molecular Genetic Analysis of FOXL2 Gene in Two Iranian Families with Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome, J Human Gen Genom. 2017 ; 1(1):e64100. doi: 10.5812/jhgg.64100.

Copyright © 2017, Journal of Human Genetics and Genomics. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited
1. Background
2. Methods
3. Results
4. Discussion
  • 1. Small KW, Stalvey M, Fisher L, Mullen L, Dickel C, Beadles K, et al. Blepharophimosis syndrome is linked to chromosome 3q. Hum Mol Genet. 1995;4(3):443-8. [PubMed: 7795600].
  • 2. Oley C, Baraitser M. Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES syndrome). J Med Genet. 1988;25(1):47-51. [PubMed: 3270326].
  • 3. Zlotogora J, Sagi M, Cohen T. The blepharophimosis, ptosis, and epicanthus inversus syndrome: delineation of two types. Am J Hum Genet. 1983;35(5):1020-7. [PubMed: 6613996].
  • 4. De Baere E. Blepharophimosis, Ptosis, and Epicanthus Inversus,. In: Pagon RA, editor. GeneReviews. Seattle; 1993.
  • 5. de Ru MH, Gille JJ, Nieuwint AW, Bijlsma JB, van der Blij JF, van Hagen JM. Interstitial deletion in 3q in a patient with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and microcephaly, mild mental retardation and growth delay: clinical report and review of the literature. Am J Med Genet A. 2005;137(1):81-7. doi: 10.1002/ajmg.a.30786. [PubMed: 16015581].
  • 6. Zahanova S, Meaney B, Labieniec B, Verdin H, De Baere E, Nowaczyk MJ. Blepharophimosis-ptosis-epicanthus inversus syndrome plus: deletion 3q22.3q23 in a patient with characteristic facial features and with genital anomalies, spastic diplegia, and speech delay. Clin Dysmorphol. 2012;21(1):48-52. doi: 10.1097/MCD.0b013e32834977f1. [PubMed: 21934608].
  • 7. Amati P, Gasparini P, Zlotogora J, Zelante L, Chomel JC, Kitzis A, et al. A gene for premature ovarian failure associated with eyelid malformation maps to chromosome 3q22-q23. Am J Hum Genet. 1996;58(5):1089-92. [PubMed: 8651270].
  • 8. Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, et al. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat Genet. 2001;27(2):159-66. doi: 10.1038/84781. [PubMed: 11175783].
  • 9. Cocquet J, Pailhoux E, Jaubert F, Servel N, Xia X, Pannetier M, et al. Evolution and expression of FOXL2. J Med Genet. 2002;39(12):916-21. [PubMed: 12471206].
  • 10. Rosenfeld MG, Briata P, Dasen J, Gleiberman AS, Kioussi C, Lin C, et al. Multistep signaling and transcriptional requirements for pituitary organogenesis in vivo. Recent Prog Horm Res. 2000;55:1-13. discussion 13-4. [PubMed: 11036930].
  • 11. Ellsworth BS, Egashira N, Haller JL, Butts DL, Cocquet J, Clay CM, et al. FOXL2 in the pituitary: molecular, genetic, and developmental analysis. Mol Endocrinol. 2006;20(11):2796-805. doi: 10.1210/me.2005-0303. [PubMed: 16840539].
  • 12. Cocquet J, De Baere E, Gareil M, Pannetier M, Xia X, Fellous M, et al. Structure, evolution and expression of the FOXL2 transcription unit. Cytogenet Genome Res. 2003;101(3-4):206-11. doi: 10.1159/000074338. [PubMed: 14684984].
  • 13. Schlessinger D, Herrera L, Crisponi L, Mumm S, Percesepe A, Pellegrini M, et al. Genes and translocations involved in POF. Am J Med Genet. 2002;111(3):328-33. doi: 10.1002/ajmg.10565. [PubMed: 12210333].
  • 14. De Baere E, Fellous M, Veitia RA. The transcription factor FOXL2 in ovarian function and dysfunction. Folia Histochem Cytobiol. 2009;47(5):S43-9. doi: 10.2478/v10042-009-0062-7. [PubMed: 20067892].
  • 15. Meduri G, Bachelot A, Duflos C, Bstandig B, Poirot C, Genestie C, et al. FOXL2 mutations lead to different ovarian phenotypes in BPES patients: Case Report. Hum Reprod. 2010;25(1):235-43. doi: 10.1093/humrep/dep355. [PubMed: 19819892].
  • 16. Fraser IS, Shearman RP, Smith A, Russell P. An association among blepharophimosis, resistant ovary syndrome, and true premature menopause. Fertil Steril. 1988;50(5):747-51. doi: 10.1016/s0015-0282(16)60309-6.
  • 17. Raile K, Stobbe H, Trobs RB, Kiess W, Pfaffle R. 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. 2005;153(3):353-8. doi: 10.1530/eje.1.01974. [PubMed: 16131596].
  • 18. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215. [PubMed: 3344216].
  • 19. De Baere E, Dixon MJ, Small KW, Jabs EW, Leroy BP, Devriendt K, et al. Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype--phenotype correlation. Hum Mol Genet. 2001;10(15):1591-600. [PubMed: 11468277].
  • 20. Jiang H, Huang X, Su Z, Rao L, Wu S, Zhang T, et al. Genetic analysis of the forkhead transcriptional factor 2 gene in three Chinese families with blepharophimosis syndrome. Mol Vis. 2013;19:418-23. [PubMed: 23441113].
  • 21. De Baere E, Beysen D, Oley C, Lorenz B, Cocquet J, De Sutter P, et al. FOXL2 and BPES: mutational hotspots, phenotypic variability, and revision of the genotype-phenotype correlation. Am J Hum Genet. 2003;72(2):478-87. doi: 10.1086/346118. [PubMed: 12529855].
  • 22. Beysen D, De Paepe A, De Baere E. FOXL2 mutations and genomic rearrangements in BPES. Hum Mutat. 2009;30(2):158-69. doi: 10.1002/humu.20807. [PubMed: 18726931].
  • 23. Haghighi A, Verdin H, Haghighi-Kakhki H, Piri N, Gohari NS, De Baere E. Missense mutation outside the forkhead domain of FOXL2 causes a severe form of BPES type II. Mol Vis. 2012;18:211-8. [PubMed: 22312189].
  • 24. Ramineni A, Coman D. De Novo 3q22. 3q24 Microdeletion in a Patient With Blepharophimosis–Ptosis–Epicanthus Inversus Syndrome, Dandy-Walker Malformation, and Wisconsin Syndrome. Child Neurol Open. 2016;3:2329048X16666362.
  • 25. Lin WD, Chou IC, Lee NC, Wang CH, Hwu WL, Lin SP, et al. FOXL2 mutations in Taiwanese patients with blepharophimosis, ptosis, epicanthus inversus syndrome. Clin Chem Lab Med. 2010;48(4):485-8. doi: 10.1515/CCLM.2010.100. [PubMed: 20184535].
  • 26. Udar N, Yellore V, Chalukya M, Yelchits S, Silva-Garcia R, Small K, et al. Comparative analysis of the FOXL2 gene and characterization of mutations in BPES patients. Hum Mutat. 2003;22(3):222-8. doi: 10.1002/humu.10251. [PubMed: 12938087].

Featured Image:

Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments