BOR AND BO SYNDROMES ARE ALLELIC DEFECTS OF EYA1

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disease cha racterized by varying combinations of branchial, otic and renal anomal ies. By positional cloning, a candidate gene, EYA1, homologous to the drosophila eyes absent gene, has recently been identified at 8q13.3 an d 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 an d BO syndromes involve the same gene was unknown. To address this ques tion, we analyzed two large independent families for which each of the 8 affected members present exclusively with BO syndrome. In both fami lies, linkage analysis mapped the causative gene to the same chromosom al region as EYA1. A search for mutations in 9 of the EYA1 coding exon s identified a 2-bp insertion segregating in one family and an X-bp de letion segregating in the other. These results demonstrate that EYA1 a lso underlies BO syndrome, and that BOR and BO syndromes are allelic d efects of this gene.