Abstract
PURPOSE: The aim of this study was to characterize the clinical presentation of atypical endothelial corneal dystrophy (ECD) and to identify possible associated genetic variants in a Chinese family. METHODS: Six affected members, 4 unaffected first-degree relatives, and 3 spouses who were enrolled in this study underwent ophthalmic examinations. Genetic linkage analysis was performed for 4 affected and 2 unaffected members, and whole-exome sequencing (WES) was performed for 2 patients to identify disease-causing variants. Candidate causal variants were verified using Sanger sequencing in family members and 200 healthy controls. RESULTS: The mean age at disease onset was 16.5 years. The early phenotype of this atypical ECD was characterized by multiple small white translucent spots located in Descemet membrane of the peripheral cornea. These spots coalesced to form opacities with variable shapes, and eventually merged along the limbus. Subsequently, translucent spots appeared in central Descemet membrane and accumulated, causing diffuse polymorphous opacities over time. Finally, significant endothelial decompensation led to diffuse corneal edema. A heterozygous missense variant in the KIAA1522 gene (c.1331G>A; p.R444Q) was identified by WES, which was present in all 6 patients but was absent in the unaffected members and healthy controls. CONCLUSIONS: The clinical features of atypical ECD are unique compared with those of known corneal dystrophies. Moreover, genetic analysis identified the c.1331G>A variant in KIAA1522 , which may be responsible for the pathogenesis of this atypical ECD. Thus, we propose this is a new form of ECD based on our clinical findings.