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

(2001) HUMAN MOLECULAR GENETICS. 10(15). p.1591-1600
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Abstract
Mutations in FOXL2, a forkhead transcription factor gene, have recently been shown to cause blepharo-phimosis-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 III 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.
Keywords
PREMATURE OVARIAN FAILURE, TRANSCRIPTION FACTOR, CHROMOSOME 3Q23, TRANSLOCATION, FKHL7, T(3-4)(Q23-P15.2), IDENTIFICATION, DUPLICATION, BREAKPOINT, ASSIGNMENT

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Citation

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MLA
De Baere, Elfride, Michael J Dixon, Kent W Small, et al. “Spectrum of FOXL2 Gene Mutations in Blepharophimosis-ptosis-epicanthus Inversus (BPES) Families Demonstrates a Genotype-phenotype Correlation.” HUMAN MOLECULAR GENETICS 10.15 (2001): 1591–1600. Print.
APA
De Baere, E., Dixon, M. J., Small, K. W., Jabs, E. W., Leroy, B., Devriendt, K., Gillerot, Y., et al. (2001). Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype-phenotype correlation. HUMAN MOLECULAR GENETICS, 10(15), 1591–1600.
Chicago author-date
De Baere, Elfride, Michael J Dixon, Kent W Small, Ethylin W Jabs, Bart Leroy, Koenraad Devriendt, Yves Gillerot, et al. 2001. “Spectrum of FOXL2 Gene Mutations in Blepharophimosis-ptosis-epicanthus Inversus (BPES) Families Demonstrates a Genotype-phenotype Correlation.” Human Molecular Genetics 10 (15): 1591–1600.
Chicago author-date (all authors)
De Baere, Elfride, Michael J Dixon, Kent W Small, Ethylin W Jabs, Bart Leroy, Koenraad Devriendt, Yves Gillerot, Geert Mortier, Françoise Meire, Lioinel Van Maldergem, Winnie Courtens, Helle Hjalgrim, Shangzhi Huang, Inge Liebaers, Nicole Van Regemorter, Philippe Touraine, Veraynth Praphanphoj, Alain Verloes, Nitin Udar, Vivek Yellore, Meenal Chalukya, Svetlana Yelchits, Anne De Paepe, Frédérique Kuttenn, Marc Fellous, Reiner Veitia, and Ludwine Messiaen. 2001. “Spectrum of FOXL2 Gene Mutations in Blepharophimosis-ptosis-epicanthus Inversus (BPES) Families Demonstrates a Genotype-phenotype Correlation.” Human Molecular Genetics 10 (15): 1591–1600.
Vancouver
1.
De Baere E, Dixon MJ, Small KW, Jabs EW, Leroy B, Devriendt K, et al. Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype-phenotype correlation. HUMAN MOLECULAR GENETICS. 2001;10(15):1591–600.
IEEE
[1]
E. De Baere et al., “Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype-phenotype correlation,” HUMAN MOLECULAR GENETICS, vol. 10, no. 15, pp. 1591–1600, 2001.
@article{315237,
  abstract     = {{Mutations in FOXL2, a forkhead transcription factor gene, have recently been shown to cause blepharo-phimosis-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 III 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.}},
  author       = {{De Baere, Elfride and Dixon, Michael J and Small, Kent W and Jabs, Ethylin W and Leroy, Bart and Devriendt, Koenraad and Gillerot, Yves and Mortier, Geert and Meire, Françoise and Van Maldergem, Lioinel and Courtens, Winnie and Hjalgrim, Helle and Huang, Shangzhi and Liebaers, Inge and Van Regemorter, Nicole and Touraine, Philippe and Praphanphoj, Veraynth and Verloes, Alain and Udar, Nitin and Yellore, Vivek and Chalukya, Meenal and Yelchits, Svetlana and De Paepe, Anne and Kuttenn, Frédérique and Fellous, Marc and Veitia, Reiner and Messiaen, Ludwine}},
  issn         = {{0964-6906}},
  journal      = {{HUMAN MOLECULAR GENETICS}},
  keywords     = {{PREMATURE OVARIAN FAILURE,TRANSCRIPTION FACTOR,CHROMOSOME 3Q23,TRANSLOCATION,FKHL7,T(3-4)(Q23-P15.2),IDENTIFICATION,DUPLICATION,BREAKPOINT,ASSIGNMENT}},
  language     = {{eng}},
  number       = {{15}},
  pages        = {{1591--1600}},
  title        = {{Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype-phenotype correlation}},
  volume       = {{10}},
  year         = {{2001}},
}

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