Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation
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Auteurs : Leilei Zhang [République populaire de Chine] ; Jie He [République populaire de Chine] ; Bing Han [République populaire de Chine] ; Linna Lu [République populaire de Chine] ; Jiayan Fan [République populaire de Chine] ; He Zhang [République populaire de Chine] ; Shengfang Ge [République populaire de Chine] ; Yixiong Zhou [République populaire de Chine] ; Renbing Jia [République populaire de Chine] ; Xianqun Fan [République populaire de Chine]Source :
- International Journal of Biological Sciences [ 1449-2288 ] ; 2016.
Abstract
Distichiasis presents as double rows of eyelashes arising from aberrant differentiation of the meibomian glands of the eyelids, and it may be sporadic or hereditary.
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DOI: 10.7150/ijbs.13774
PubMed: 27570485
PubMed Central: 4997055
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Novel <italic>FOXC2</italic> Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation</title><author><name sortKey="Zhang, Leilei" sort="Zhang, Leilei" uniqKey="Zhang L" first="Leilei" last="Zhang">Leilei Zhang</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="He, Jie" sort="He, Jie" uniqKey="He J" first="Jie" last="He">Jie He</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Han, Bing" sort="Han, Bing" uniqKey="Han B" first="Bing" last="Han">Bing Han</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of endocrinology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of endocrinology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Lu, Linna" sort="Lu, Linna" uniqKey="Lu L" first="Linna" last="Lu">Linna Lu</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Fan, Jiayan" sort="Fan, Jiayan" uniqKey="Fan J" first="Jiayan" last="Fan">Jiayan Fan</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, He" sort="Zhang, He" uniqKey="Zhang H" first="He" last="Zhang">He Zhang</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Ge, Shengfang" sort="Ge, Shengfang" uniqKey="Ge S" first="Shengfang" last="Ge">Shengfang Ge</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Yixiong" sort="Zhou, Yixiong" uniqKey="Zhou Y" first="Yixiong" last="Zhou">Yixiong Zhou</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Jia, Renbing" sort="Jia, Renbing" uniqKey="Jia R" first="Renbing" last="Jia">Renbing Jia</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Fan, Xianqun" sort="Fan, Xianqun" uniqKey="Fan X" first="Xianqun" last="Fan">Xianqun Fan</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27570485</idno><idno type="pmc">4997055</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997055</idno><idno type="RBID">PMC:4997055</idno><idno type="doi">10.7150/ijbs.13774</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">003F39</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003F39</idno><idno type="wicri:Area/Pmc/Curation">003F38</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">003F38</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Novel <italic>FOXC2</italic> Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation</title><author><name sortKey="Zhang, Leilei" sort="Zhang, Leilei" uniqKey="Zhang L" first="Leilei" last="Zhang">Leilei Zhang</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="He, Jie" sort="He, Jie" uniqKey="He J" first="Jie" last="He">Jie He</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Han, Bing" sort="Han, Bing" uniqKey="Han B" first="Bing" last="Han">Bing Han</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of endocrinology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of endocrinology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Lu, Linna" sort="Lu, Linna" uniqKey="Lu L" first="Linna" last="Lu">Linna Lu</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Fan, Jiayan" sort="Fan, Jiayan" uniqKey="Fan J" first="Jiayan" last="Fan">Jiayan Fan</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, He" sort="Zhang, He" uniqKey="Zhang H" first="He" last="Zhang">He Zhang</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Ge, Shengfang" sort="Ge, Shengfang" uniqKey="Ge S" first="Shengfang" last="Ge">Shengfang Ge</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Yixiong" sort="Zhou, Yixiong" uniqKey="Zhou Y" first="Yixiong" last="Zhou">Yixiong Zhou</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Jia, Renbing" sort="Jia, Renbing" uniqKey="Jia R" first="Renbing" last="Jia">Renbing Jia</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author><author><name sortKey="Fan, Xianqun" sort="Fan, Xianqun" uniqKey="Fan X" first="Xianqun" last="Fan">Xianqun Fan</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea></affiliation></author></analytic><series><title level="j">International Journal of Biological Sciences</title><idno type="eISSN">1449-2288</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Distichiasis presents as double rows of eyelashes arising from aberrant differentiation of the meibomian glands of the eyelids, and it may be sporadic or hereditary. <italic>FOXC2</italic> gene mutations in hereditary distichiasis are rarely reported. Here, we examined two generations of a Chinese family with hereditary distichiasis but without lymphedema or other features of LD syndrome. The <italic>FOXC2</italic> gene was amplified and sequenced in all family members. Subcellular localization and luciferase assays were performed to assess the activity of the mutant FOXC2 protein. Clinical examinations showed distichiasis, lower eyelid ectropion, congenital ptosis and photophobia in all affected individuals. Sequence analysis revealed a novel frameshift mutation, c.964_965insG, in the coding region of the<italic> FOXC2</italic> gene. This mutation caused protein truncation due to the presence of a premature stop codon. A fluorescence assay showed that this mutation did not change the nuclear localization of the protein. However, it impaired DNA-binding activity and decreased transcriptional activation. This is the first report of a <italic>FOXC2 </italic>mutation in hereditary distichiasis in the Chinese population. The findings of our study expand the <italic>FOXC2</italic> mutation spectrum and contribute to the understanding of the genotype-phenotype correlation of this disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Vreeburg, M" uniqKey="Vreeburg M">M Vreeburg</name></author><author><name sortKey="Heitink, Mv" uniqKey="Heitink M">MV Heitink</name></author><author><name sortKey="Damstra, Rj" uniqKey="Damstra R">RJ Damstra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mellor, Rh" uniqKey="Mellor R">RH Mellor</name></author><author><name sortKey="Brice, G" uniqKey="Brice G">G Brice</name></author><author><name sortKey="Stanton, Aw" uniqKey="Stanton A">AW Stanton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mangion, J" uniqKey="Mangion J">J Mangion</name></author><author><name sortKey="Rahman, N" uniqKey="Rahman N">N Rahman</name></author><author><name sortKey="Mansour, S" uniqKey="Mansour S">S Mansour</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yabuki, S" uniqKey="Yabuki S">S Yabuki</name></author><author><name sortKey="Kikuchi, S" uniqKey="Kikuchi S">S Kikuchi</name></author><author><name sortKey="Ikegawa, S" uniqKey="Ikegawa S">S Ikegawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Traboulsi, Ei" uniqKey="Traboulsi E">EI Traboulsi</name></author><author><name sortKey="Al Khayer, K" uniqKey="Al Khayer K">K Al-Khayer</name></author><author><name sortKey="Matsumoto, M" uniqKey="Matsumoto M">M Matsumoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Patil, Bb" uniqKey="Patil B">BB Patil</name></author><author><name sortKey="Bell, R" uniqKey="Bell R">R Bell</name></author><author><name sortKey="Brice, G" uniqKey="Brice G">G Brice</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brooks, Bp" uniqKey="Brooks B">BP Brooks</name></author><author><name sortKey="Dagenais, Sl" uniqKey="Dagenais S">SL Dagenais</name></author><author><name sortKey="Nelson, Cc" uniqKey="Nelson C">CC Nelson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Jia, R" uniqKey="Jia R">R Jia</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saleem, Ra" uniqKey="Saleem R">RA Saleem</name></author><author><name sortKey="Banerjee Basu, S" uniqKey="Banerjee Basu S">S Banerjee-Basu</name></author><author><name sortKey="Berry, Fb" uniqKey="Berry F">FB Berry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berry, Fb" uniqKey="Berry F">FB Berry</name></author><author><name sortKey="Tamimi, Y" uniqKey="Tamimi Y">Y Tamimi</name></author><author><name sortKey="Carle, Mv" uniqKey="Carle M">MV Carle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roy, A" uniqKey="Roy A">A Roy</name></author><author><name sortKey="Kucukural, A" uniqKey="Kucukural A">A Kucukural</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carlsson, P" uniqKey="Carlsson P">P Carlsson</name></author><author><name sortKey="Mahlapuu, M" uniqKey="Mahlapuu M">M Mahlapuu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Katoh, M" uniqKey="Katoh M">M Katoh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lines, Ma" uniqKey="Lines M">MA Lines</name></author><author><name sortKey="Kozlowski, K" uniqKey="Kozlowski K">K Kozlowski</name></author><author><name sortKey="Walter, Ma" uniqKey="Walter M">MA Walter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ito, Ya" uniqKey="Ito Y">YA Ito</name></author><author><name sortKey="Goping, Is" uniqKey="Goping I">IS Goping</name></author><author><name sortKey="Berry, F" uniqKey="Berry F">F Berry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, Rf" uniqKey="Du R">RF Du</name></author><author><name sortKey="Huang, H" uniqKey="Huang H">H Huang</name></author><author><name sortKey="Fan, Ll" uniqKey="Fan L">LL Fan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Semina, Ev" uniqKey="Semina E">EV Semina</name></author><author><name sortKey="Brownell, I" uniqKey="Brownell I">I Brownell</name></author><author><name sortKey="Mintz Hittner, Ha" uniqKey="Mintz Hittner H">HA Mintz-Hittner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Islam, L" uniqKey="Islam L">L Islam</name></author><author><name sortKey="Kelberman, D" uniqKey="Kelberman D">D Kelberman</name></author><author><name sortKey="Williamson, L" uniqKey="Williamson L">L Williamson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crisponi, L" uniqKey="Crisponi L">L Crisponi</name></author><author><name sortKey="Deiana, M" uniqKey="Deiana M">M Deiana</name></author><author><name sortKey="Loi, A" uniqKey="Loi A">A Loi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fan, J" uniqKey="Fan J">J Fan</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Huang, X" uniqKey="Huang X">X Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Laissue, P" uniqKey="Laissue P">P Laissue</name></author><author><name sortKey="Lakhal, B" uniqKey="Lakhal B">B Lakhal</name></author><author><name sortKey="Benayoun, Ba" uniqKey="Benayoun B">BA Benayoun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berry, Fb" uniqKey="Berry F">FB Berry</name></author><author><name sortKey="Saleem, Ra" uniqKey="Saleem R">RA Saleem</name></author><author><name sortKey="Walter, Ma" uniqKey="Walter M">MA Walter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fujita, H" uniqKey="Fujita H">H Fujita</name></author><author><name sortKey="Kang, M" uniqKey="Kang M">M Kang</name></author><author><name sortKey="Eren, M" uniqKey="Eren M">M Eren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sutkowska, E" uniqKey="Sutkowska E">E Sutkowska</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Steensel, Ma" uniqKey="Van Steensel M">MA van Steensel</name></author><author><name sortKey="Damstra, Rj" uniqKey="Damstra R">RJ Damstra</name></author><author><name sortKey="Heitink, Mv" uniqKey="Heitink M">MV Heitink</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jeffery, S" uniqKey="Jeffery S">S Jeffery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brice, G" uniqKey="Brice G">G Brice</name></author><author><name sortKey="Mansour, S" uniqKey="Mansour S">S Mansour</name></author><author><name sortKey="Bell, R" uniqKey="Bell R">R Bell</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Biol Sci</journal-id><journal-id journal-id-type="iso-abbrev">Int. J. Biol. Sci</journal-id><journal-id journal-id-type="publisher-id">ijbs</journal-id><journal-title-group><journal-title>International Journal of Biological Sciences</journal-title></journal-title-group><issn pub-type="epub">1449-2288</issn><publisher><publisher-name>Ivyspring International Publisher</publisher-name><publisher-loc>Sydney</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27570485</article-id><article-id pub-id-type="pmc">4997055</article-id><article-id pub-id-type="doi">10.7150/ijbs.13774</article-id><article-id pub-id-type="publisher-id">ijbsv12p1114</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>Novel <italic>FOXC2</italic> Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Leilei</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>He</surname><given-names>Jie</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Han</surname><given-names>Bing</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Lu</surname><given-names>Linna</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Fan</surname><given-names>Jiayan</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>He</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ge</surname><given-names>Shengfang</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zhou</surname><given-names>Yixiong</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="corresp" rid="FNA_envelop">✉</xref></contrib><contrib contrib-type="author"><name><surname>Jia</surname><given-names>Renbing</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="corresp" rid="FNA_envelop">✉</xref></contrib><contrib contrib-type="author"><name><surname>Fan</surname><given-names>Xianqun</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="corresp" rid="FNA_envelop">✉</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China</aff><aff id="A2"><label>2</label>Department of endocrinology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.</aff><author-notes><corresp id="FNA_envelop">✉ Corresponding authors: Tel./fax: +86 21 63135606 <email>fanxq@sh163.net</email> (XQ. Fan) Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, P.R. China.</corresp><fn fn-type="equal" id="FNA_star"><p><sup>* </sup>These authors contributed equally.</p></fn><fn fn-type="COI-statement"><p>Competing Interests: The authors have declared that no competing interest exists.</p></fn></author-notes><pub-date pub-type="collection"><year>2016</year></pub-date><pub-date pub-type="epub"><day>6</day><month>8</month><year>2016</year></pub-date><volume>12</volume><issue>9</issue><fpage>1114</fpage><lpage>1120</lpage><history><date date-type="received"><day>6</day><month>9</month><year>2015</year></date><date date-type="accepted"><day>6</day><month>7</month><year>2016</year></date></history><permissions><copyright-statement>© Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.</copyright-statement><copyright-year>2016</copyright-year></permissions><abstract><p>Distichiasis presents as double rows of eyelashes arising from aberrant differentiation of the meibomian glands of the eyelids, and it may be sporadic or hereditary. <italic>FOXC2</italic> gene mutations in hereditary distichiasis are rarely reported. Here, we examined two generations of a Chinese family with hereditary distichiasis but without lymphedema or other features of LD syndrome. The <italic>FOXC2</italic> gene was amplified and sequenced in all family members. Subcellular localization and luciferase assays were performed to assess the activity of the mutant FOXC2 protein. Clinical examinations showed distichiasis, lower eyelid ectropion, congenital ptosis and photophobia in all affected individuals. Sequence analysis revealed a novel frameshift mutation, c.964_965insG, in the coding region of the<italic> FOXC2</italic> gene. This mutation caused protein truncation due to the presence of a premature stop codon. A fluorescence assay showed that this mutation did not change the nuclear localization of the protein. However, it impaired DNA-binding activity and decreased transcriptional activation. This is the first report of a <italic>FOXC2 </italic>mutation in hereditary distichiasis in the Chinese population. The findings of our study expand the <italic>FOXC2</italic> mutation spectrum and contribute to the understanding of the genotype-phenotype correlation of this disease.</p></abstract><kwd-group><kwd>congenital distichiasis</kwd><kwd><italic> FOXC2</italic></kwd><kwd>mutation.</kwd></kwd-group></article-meta></front><floats-group><fig id="F1" position="float"><label>Figure 1</label><caption><p>(A) Pedigree of the family with distichiasis. Squares and circles represent males and females, respectively. The shaded symbols indicate the presence of distichiasis. Unaffected individuals are depicted by unshaded symbols. (B) Images of the three affected pedigree members. Both I-1 and II-1 had blepharoptosis, and II-2 had epicanthus. (C) Details of eyes with distichiasis. Note the double row of eyelashes originating from the inner margin of the eyelids, as indicated by the black arrows (II-2). (D) Images of the proband after fluorescein staining, as visualized using a slit lamp. The green fluorescence indicates the corneal injuries in the right and left eyes (II-2).</p></caption><graphic xlink:href="ijbsv12p1114g001"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><p>(A) The normal and mutated sequences are shown separately and were detected by Sanger sequencing. (B) A fluorescence assay demonstrated that the mutant plasmid (the lower plate), but not the wild type plasmid (the upper plate), resulted in nuclear aggregation after transfection with EGFP tags. (C) The DNA-FOXC2 binding activity was detected by EMSA. DNA-FOXC2 protein complexes are indicated by asterisk, which mark the shift band. The non-specific antibody isogenic IgG was used as the control. It could not form the DNA protein complexes. The super-shift band contained the DNA probe, the nuclear protein and the anti-FOXC2 antibody, which represented the specificity of the EMSA. The negative control was the lane that only contained the labeled probes. The positive control was the lane that contained the samples and the labeled probes. Competitor 1, competitor 2 and competitor 3 (1 μM, 30 μM and 90 μM, respectively) represent increased concentrations of unlabeled specific probe, which were used to compete with the sample and with FOXC2-DNA binding. The bottom bands indicate free probe. (D) Transactivation assays were performed using 293T cells transfected with a luciferase reporter along with wild type and mutant <italic>FOXC2</italic> constructs. Luciferase values were normalized to Renilla luciferase. Mean luciferase values from a representative experiment with transfection in triplicate are presented. The error bars correspond to the standard error of the mean (P<0.05).</p></caption><graphic xlink:href="ijbsv12p1114g002"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><p>Conservation analysis of FOXC2 indicated that the FOXC2 amino acid sequence is partly evolutionarily conserved in <italic>Homo sapiens</italic>, <italic>Equus caballus</italic>, <italic>Mus musculus</italic> and <italic>Rattus norvegicus</italic>. The arrow indicates the 322<sup>nd</sup> amino acid.</p></caption><graphic xlink:href="ijbsv12p1114g003"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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