Novel FOXL2 variants in two Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndrome
Introduction: Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a rare inherited disorder. This study was aimed to identify and functionally validate FOXL2 variants in two Chinese families with BPES.Methods: The proband and his family members were subjected to whole-exome sequenci...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1343411/full |
| _version_ | 1827263144591884288 |
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| author | Mingyu Zhao Xiaolu Meng Jiaqi Wang Tailing Wang |
| author_facet | Mingyu Zhao Xiaolu Meng Jiaqi Wang Tailing Wang |
| author_sort | Mingyu Zhao |
| collection | DOAJ |
| description | Introduction: Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a rare inherited disorder. This study was aimed to identify and functionally validate FOXL2 variants in two Chinese families with BPES.Methods: The proband and his family members were subjected to whole-exome sequencing to identify disease-associated variants. Several bioinformatic tools were used to computationally predict altered proteins. In vitro functional assays were conducted by transfecting wild-type and mutant FOXL2 cDNAs into HEK-293 cells, followed by subcellular localization assays, luciferase reporter gene assays, and quantitative real-time polymerase chain reaction.Results: The clinical features of BPES, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus, were present in all affected patients. Two novel mutations were detected, c.292T>A and c.383G>T. Whole-exome sequencing analysis and prediction software suggested that these mutations were pathogenic. Functional studies showed that these two point mutations decreased FOXL2 protein expression, resulting in subcellular mislocalization and aberrant transcriptional activity of the steroidogenic acute regulatory protein gene promoter.Conclusion: Our results add to the current understanding of known FOXL2 variants in, and our in vitro experiments provide reference data and insights into the etiology of BPES. Further studies are needed to identify the possible mechanisms underlying the action of this mutation on the development of BPES. |
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| last_indexed | 2025-03-22T03:25:30Z |
| publishDate | 2024-02-01 |
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| spelling | doaj.art-418e1cbf864e466093712e5e49e6106e2024-04-29T09:02:05ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-02-011510.3389/fgene.2024.13434111343411Novel FOXL2 variants in two Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndromeMingyu Zhao0Xiaolu Meng1Jiaqi Wang2Tailing Wang3The Department of Facial and Neck Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaPlastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaThe Department of Facial and Neck Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaThe Department of Facial and Neck Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaIntroduction: Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a rare inherited disorder. This study was aimed to identify and functionally validate FOXL2 variants in two Chinese families with BPES.Methods: The proband and his family members were subjected to whole-exome sequencing to identify disease-associated variants. Several bioinformatic tools were used to computationally predict altered proteins. In vitro functional assays were conducted by transfecting wild-type and mutant FOXL2 cDNAs into HEK-293 cells, followed by subcellular localization assays, luciferase reporter gene assays, and quantitative real-time polymerase chain reaction.Results: The clinical features of BPES, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus, were present in all affected patients. Two novel mutations were detected, c.292T>A and c.383G>T. Whole-exome sequencing analysis and prediction software suggested that these mutations were pathogenic. Functional studies showed that these two point mutations decreased FOXL2 protein expression, resulting in subcellular mislocalization and aberrant transcriptional activity of the steroidogenic acute regulatory protein gene promoter.Conclusion: Our results add to the current understanding of known FOXL2 variants in, and our in vitro experiments provide reference data and insights into the etiology of BPES. Further studies are needed to identify the possible mechanisms underlying the action of this mutation on the development of BPES.https://www.frontiersin.org/articles/10.3389/fgene.2024.1343411/fullBlepharophimosis-ptosis-epicanthus inversus syndromeFOXL2 variantwhole exome sequencingtansfectionprotein model prediction |
| spellingShingle | Mingyu Zhao Xiaolu Meng Jiaqi Wang Tailing Wang Novel FOXL2 variants in two Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndrome Frontiers in Genetics Blepharophimosis-ptosis-epicanthus inversus syndrome FOXL2 variant whole exome sequencing tansfection protein model prediction |
| title | Novel FOXL2 variants in two Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndrome |
| title_full | Novel FOXL2 variants in two Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndrome |
| title_fullStr | Novel FOXL2 variants in two Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndrome |
| title_full_unstemmed | Novel FOXL2 variants in two Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndrome |
| title_short | Novel FOXL2 variants in two Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndrome |
| title_sort | novel foxl2 variants in two chinese families with blepharophimosis ptosis and epicanthus inversus syndrome |
| topic | Blepharophimosis-ptosis-epicanthus inversus syndrome FOXL2 variant whole exome sequencing tansfection protein model prediction |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1343411/full |
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