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Seven Novel and Three Known Mutations in FOXL2 in 10 Chinese Families with Blepharophimosis Syndrome

[ Vol. 18 , Issue. 3 ]

Author(s):

B. Lin, B. Zeng, J. Zhao, T. Xu, Y. Wang, B. Hu, F. Li, Q. Zhao, R. Liu, J. Liu, J.M. Chen, D. Huang* and Y. Wang*   Pages 152 - 159 ( 8 )

Abstract:


Background: Blepharophimosis syndrome (BPES) is characterized by eyelid malformation with occasional premature ovarian failure. Mutations in FOXL2 underlie a fraction of BPES cases.

Objective: We aimed to investigate the genetic basis of BPES in 26 Chinese families that included 78 patients.

Methods: We performed ophthalmological examinations on each family member. We used Sanger sequencing to screen FOXL2 exons and their flanking sequences. We also performed bioinformatics studies, structural modeling and pathogenicity evaluations on all identified variations. Literature was reviewed and genotype-phenotype correlation analysis was performed.

Results: The patients had typical manifestations of BPES. Ten mutations were identified in ten of the twenty-six families. Among these, seven were novel mutations. These included the six truncating mutations, p.Glu69*, p.Gly256Glyfs*14, p.Ala14Serfs*135, p.Pro333Profs*200, p.Pro290Leufs*70, and p.Pro157Profs*91, and one missense mutation, p.Tyr59Cys. The mutations were scattered within the gene, and no mutational hotspots were found. Genotype-phenotype correlation analysis showed that frameshift or nonsense mutations were correlated with type I BPES, while in-frame or missense mutations were associated with type II BPES.

Conclusion: We report the largest BPES cohort in China thus far as well as seven novel mutations in FOXL2. The identification of novel mutations has not only expanded the mutational spectrum of the gene (which is valuable for mutation detection-based screening) but also suggests that most mutations within the Chinese population may not have been characterized yet.

Keywords:

Blepharophimosis syndrome, BPES, FOXL2, ophthalmology, mutation, structural modeling.

Affiliation:

Oculoplasty Department, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yatsen University, Guangzhou, Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, Oculoplasty Department, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yatsen University, Guangzhou, State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Fetal Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Fifth Affiliated Hospital, Sun Yat-sen University-BGI Laboratory, Department of Experimental Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Department of Prenatal Diagnostic Center, Guangzhou Women and Children`s Medical Centre, Guangzhou Medical University, Guangzhou, Department of Obstetrics and Gynecology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, Guangdong 529030, Fifth Affiliated Hospital, Sun Yat-sen University-BGI Laboratory, Department of Experimental Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Institut National de la Sante et de la Recherche Medicale (INSERM), Brest, Oculoplasty Department, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yatsen University, Guangzhou, Xinhua College, Sun Yat-sen University, Guangzhou



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