A Single-Base Substitution in the Seed Region of miR-184 Causes EDICT Syndrome

PURPOSE. To investigate the cause of the syndrome characterized by endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT). METHODS. Previously a multigenerational family was reported that comprised 10 individuals affected by syndromal anterior segment dysgenesis. Blood samples were re-collected from eight affected and two unaffected individuals, and genomic DNA was extracted. A total of 24 candidate genes and 4 microRNAs residing within the critical interval were sequenced bidirectionally. In silico analyses were performed to examine the effect of the causal variant on the stability of the pre-microRNA structure. RESULTS. Bidirectional sequencing identified the single-base substitution +57C > T in miR-184. This variation segregated with the disease phenotype and was absent in the 1000 Genomes project, 1130 control chromosomes, and 28 nonhuman vertebrates. CONCLUSIONS. The single-base-pair substitution in the seed region of miR-184 is responsible for the disease phenotype observed in EDICT syndrome. (Invest Ophthalmol Vis Sci. 2012; 53: 348-353) DOI:10.1167/iovs.11-8783