Abstract
The molecular basis for cornea guttata and anterior polar cataract remains idiopathic in most cases. In this study, our aim was to identify the disease-associated gene in Chinese patients with these conditions. Patients with the conditions from two Chinese families, and ten sporadic patients, were investigated. Genome-wide linkage and exome sequencing analyses showed transmembrane and coiled-coil domain 3 (TMCO3) as the disease candidate gene for a coding heterozygous mutation c.41C > T, resulting in a P14L amino acid change that co-segregated with the disease phenotype as discovered in Family A. TMCO3 belongs to the monovalent cation: protein antiporter 2 transporter family, a moderately large group whose members all share a very similar function under normal physiological conditions. The gene is expressed in the human cornea, lens capsule, and choroid-retinal pigment epithelium. This study reveals, for the first time, that mutations in TMCO3 are associated with cornea guttata and anterior polar cataract, warranting further investigation into the pathogenesis of this disorder.