Abstract
Purpose :
To describe two sporadic Mexican patients suffering from congenital bilateral, total sclerocornea, aphakia, and microphthalmia with the identification of two novel biallelic mutations in the FOXE3 gene.
Methods :
Two affected individuals with congenital bilateral, total sclerocornea, aphakia and microphthalmia underwent detailed examinations by ophthalmologists including slit lamp examination, visual acuity measurements, and intraocular pressure measurements. Ocular ultrasonography and ultrasound biomicroscopy (UBM) were performed in each affected individual. Genomic DNA was isolated from blood leukocytes in each subject and molecular analysis of Forkhead box protein E3 (FOXE3) mutation was performed with PCR amplification and direct DNA sequencing. For cosegregation analysis, presumable pathogenic variants were tested by Sanger sequencing in patients’ parents.
Results :
Molecular analysis of FOXE3 was performed in 2 cases with congenital bilateral, total sclerocornea, aphakia and microphthalmia. Parents of patient #1 were consanguineous and FOXE3 gene analysis demonstrated a novel a c.291C>G (p.Ile97Met) pathogenic variant. In patient #2, compound heterozygosity for the novel c.387C>G (p.Phe129Leu) transversion and for the previously reported c.244A>G (p.Met82Val) transition, was recognized.
Conclusions :
The sclerocornea-microphthalmia-aphakia complex is a severe malformative ocular phenotype resulting from biallelic mutations in the FOXE3 gene. To date, patients from 14 families with this uncommon ocular disorder have been described, most of them from consanguineous Asian pedigrees. In the present study, we describe 2 sporadic Mexican patients suffering from congenital bilateral, total sclerocornea, aphakia, and microphthalmia. The identification of two novel pathogenic variants expands the mutational spectrum in FOXE3-related congenital eye disorders. In addition, we performed a review of the clinical and genotypic characteristics of all published patients carrying biallelic FOXE3 mutations.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.