BOR and BO syndromes are allelic defects of EYA1.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disease characterized by varying combinations of branchial, otic and renal anomalies. By positional cloning, a candidate gene, EYA1, homologous to the drosophila eyes absent gene, has recently been identified at 8q13.3 and shown to underlie this syndrome. The name branchio-oto (BO) syndrome has been used to describe a similar combination of branchial and otic anomalies, without the association of renal anomalies. Whether BOR and BO syndromes involve the same gene was unknown. To address this question, we analyzed two large independent families for which each of the 8 affected members present exclusively with BO syndrome. In both families, linkage analysis mapped the causative gene to the same chromosomal region as EYA1. A search for mutations in 9 of the EYA1 coding exons identified a 2-bp insertion segregating in one family and an 8-bp deletion segregating in the other. These results demonstrate that EYA1 also underlies BO syndrome, and that BOR and BO syndromes are allelic defects of this gene.