Figure 3.

Molecular analysis of the Mexican pedigree. A: Sequencing chromatogram showing the c.292T>C mutation in the FOXE3 gene in an affected member of the Mexican pedigree. B: Protein sequence conservation. Diagram showing part of the amino acid sequence of the FOXE3 protein within the forkhead domain. Note the evolutionary conserved tyrosine (Y) residue in the normal sequence that is mutated to a histidine in the patients with sclerocornea. The F93 and F98 residues that are mutated to give rise to the dysgenetic lens mouse mutant are also depicted. C: Structural model of the forkhead domain of human FOXE3 wildtype and p.Y98H. (i) Ribbon representation of the DNA – fork head domain complex. DNA is depicted in gray and forkhead domain in red, yellow or green depending if helix, beta strand or loop regions. Structural microenvironment of Y98 (ii) and H98 (iii), residues within 6 Angstrom of Y98, or H98, is shown in stick representation and labeled in black boxes. (iv) Structural overlay of wild type (Y98) and mutant (H98). Figures were generated using PyMOL.