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A novel variant of the FOXC1 gene causes Axenfeld-Rieger syndrome with congenital glaucoma in a Chinese boy
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  • Min Tang,
  • Kaiming Li,
  • Qi Zhou,
  • Jinchuan Wu,
  • Yang Cao,
  • Xiaohong Xiang,
  • Yingqing Lei,
  • Min Tian,
  • Lu Guo,
  • Yinggui Yu,
  • Hongbin LV
Min Tang
The Affiliated Hospital of Southwest Medical University
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Kaiming Li
The Affiliated Hospital of Southwest Medical University
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Qi Zhou
The Affiliated Hospital of Southwest Medical University
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Jinchuan Wu
The Affiliated Hospital of Southwest Medical University
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Yang Cao
The Affiliated Hospital of Southwest Medical University
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Xiaohong Xiang
The Affiliated Hospital of Southwest Medical University
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Yingqing Lei
The Affiliated Hospital of Southwest Medical University
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Min Tian
The Affiliated Hospital of Southwest Medical University
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Lu Guo
The Affiliated Hospital of Southwest Medical University
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Yinggui Yu
The Affiliated Hospital of Southwest Medical University
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Hongbin LV
The Affiliated Hospital of Southwest Medical University
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Abstract

Axenfeld-Rieger syndrome is an autosomal dominant genetic disease characterized by binocular anterior segment development defects and systemic dysplasia. In our study, a Chinese Axenfeld-Rieger syndrome pedigree was analyzed. After obtaining consent from the subjects, ophthalmic examinations were performed, and blood samples were collected. Then, the causative gene was identified by targeted next-generation sequencing, and candidate mutations were verified by Sanger sequencing. Pathogenicity analysis and conservative analysis were performed on the mutant gene to evaluate its pathogenicity, and SWISS-MODEL was used to construct the three-dimensional structure of the FOXC1 region to predict the effect of mutations on the structure of the FOXC1 protein. Optimistically, a novel heterozygous, deleterious variant of the FOXC1 gene, c.246C>A(p.S82R), was successfully identified in this Axenfeld-Rieger syndrome pedigree, which cosegregated with the clinical phenotype. This variant resulted in the mutation of amino acid 82 from serine to arginine. The evolution of serine(s) in different species was highly conserved. This mutation led to a change in the three-dimensional structure of the protein, which was pathogenic. The discovery of these new mutation sites further expands its mutation spectrum. Our understanding of Axenfeld-Rieger syndrome will facilitate the development of methods for the diagnosis, prevention and genetic counseling of this disease.