Mutations of a human homologue of the Drosophila eyes absent gene (EYA1) detected in patients with congenital cataracts and ocular anterior segment anomalies.

The Drosophila eyes absent gene ( eya ) is involved in the formation of compound eyes. Flies with loss-of-function mutations of this gene develop no eyes and form the ectopic eye in the antennae and the ventral zone of the head on target expression. A highly conserved homo-logous gene in various invertebrates and vertebrates has been shown to function in the formation of the eye. In contrast, a human homologue, EYA1, has been identified by positional cloning as a candidate gene for branchio-oto-renal (BOR) syndrome, in which phenotypic manifestations are restricted to the areas of branchial arch, ear and kidney, with usually no anomalies in the eye. We have examined genomic DNA isolated from patients with various types of developmental eye anomaly for EYA1 mutations by the use of polymerase chain reaction-single-strand conformation polymorphism and sequencing. We identified three novel missense mutations in patients who had con-genital cataracts and ocular anterior segment anomalies. One of the patients had clinical features of BOR syndrome as well. This result implies that the human EYA1 gene is also involved in eye morphogenesis, and that a wide variety of clinical manifestations may be caused by EYA1 mutations.