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Novel FOXL2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency

BACKGROUND: Blepharophimosis‐ptosis‐epicanthus inversus syndrome (BPES) is a malformation of the eyelids. Forkhead Box L2 (FOXL2) is the only gene known to be associated with BPES. METHODS: We identified two Han Chinese BPES families with premature ovarian insufficiency (POI). Sanger sequencing and...

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Autores principales: Yang, Xiao‐Wen, He, Wen‐Bin, Gong, Fei, Li, Wen, Li, Xiu‐Rong, Zhong, Chang‐Gao, Lu, Guang‐Xiu, Lin, Ge, Du, Juan, Tan, Yue‐Qiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902393/
https://www.ncbi.nlm.nih.gov/pubmed/29378385
http://dx.doi.org/10.1002/mgg3.366
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author Yang, Xiao‐Wen
He, Wen‐Bin
Gong, Fei
Li, Wen
Li, Xiu‐Rong
Zhong, Chang‐Gao
Lu, Guang‐Xiu
Lin, Ge
Du, Juan
Tan, Yue‐Qiu
author_facet Yang, Xiao‐Wen
He, Wen‐Bin
Gong, Fei
Li, Wen
Li, Xiu‐Rong
Zhong, Chang‐Gao
Lu, Guang‐Xiu
Lin, Ge
Du, Juan
Tan, Yue‐Qiu
author_sort Yang, Xiao‐Wen
collection PubMed
description BACKGROUND: Blepharophimosis‐ptosis‐epicanthus inversus syndrome (BPES) is a malformation of the eyelids. Forkhead Box L2 (FOXL2) is the only gene known to be associated with BPES. METHODS: We identified two Han Chinese BPES families with premature ovarian insufficiency (POI). Sanger sequencing and in vitro functional analysis were performed to identify the genetic cause. RESULTS: Sanger sequencing identified two novel mutations (c.462_468del, c.988_989insG) in FOXL2, one in each family. The in vitro functional analysis confirmed that both novel mutations were associated with impaired transactivation of downstream genes. Specifically, the single‐base insertion, c.988_989insG, led to subcellular mislocalization and aggregation of the encoded protein, which validated the hypothesis that the two novel FOXL2 mutations are deleterious and associated with POI in the two BPES families. CONCLUSION: The novel mutations identified in the present study will enhance the present knowledge of the mutation spectrum of FOXL2. The in vitro experiments provide further insights into the molecular mechanism by which the two new variants mediate disease pathogenesis and may contribute to elucidating the genotype‐phenotype correlation between the two novel FOXL2 mutations and POI.
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spelling pubmed-59023932018-04-24 Novel FOXL2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency Yang, Xiao‐Wen He, Wen‐Bin Gong, Fei Li, Wen Li, Xiu‐Rong Zhong, Chang‐Gao Lu, Guang‐Xiu Lin, Ge Du, Juan Tan, Yue‐Qiu Mol Genet Genomic Med Original Articles BACKGROUND: Blepharophimosis‐ptosis‐epicanthus inversus syndrome (BPES) is a malformation of the eyelids. Forkhead Box L2 (FOXL2) is the only gene known to be associated with BPES. METHODS: We identified two Han Chinese BPES families with premature ovarian insufficiency (POI). Sanger sequencing and in vitro functional analysis were performed to identify the genetic cause. RESULTS: Sanger sequencing identified two novel mutations (c.462_468del, c.988_989insG) in FOXL2, one in each family. The in vitro functional analysis confirmed that both novel mutations were associated with impaired transactivation of downstream genes. Specifically, the single‐base insertion, c.988_989insG, led to subcellular mislocalization and aggregation of the encoded protein, which validated the hypothesis that the two novel FOXL2 mutations are deleterious and associated with POI in the two BPES families. CONCLUSION: The novel mutations identified in the present study will enhance the present knowledge of the mutation spectrum of FOXL2. The in vitro experiments provide further insights into the molecular mechanism by which the two new variants mediate disease pathogenesis and may contribute to elucidating the genotype‐phenotype correlation between the two novel FOXL2 mutations and POI. John Wiley and Sons Inc. 2018-01-29 /pmc/articles/PMC5902393/ /pubmed/29378385 http://dx.doi.org/10.1002/mgg3.366 Text en © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Yang, Xiao‐Wen
He, Wen‐Bin
Gong, Fei
Li, Wen
Li, Xiu‐Rong
Zhong, Chang‐Gao
Lu, Guang‐Xiu
Lin, Ge
Du, Juan
Tan, Yue‐Qiu
Novel FOXL2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency
title Novel FOXL2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency
title_full Novel FOXL2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency
title_fullStr Novel FOXL2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency
title_full_unstemmed Novel FOXL2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency
title_short Novel FOXL2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency
title_sort novel foxl2 mutations cause blepharophimosis‐ptosis‐epicanthus inversus syndrome with premature ovarian insufficiency
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902393/
https://www.ncbi.nlm.nih.gov/pubmed/29378385
http://dx.doi.org/10.1002/mgg3.366
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