A novel variant of the FOXC1 gene causes Axenfeld-Rieger syndrome with
congenital glaucoma in a Chinese boy
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.