Branchio-oto-renal syndrome: identification of a novel mutation in the EYA1 gene.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by the association of branchial cysts or fistulae, external ear malformation and/or preauricular pits, hearing loss, and renal anomalies. Mutations in the EYA1 gene, a human homologue of the Drosophila 'eyes absent' gene, have been identified as cause of the syndrome. We report here two families with BOR syndrome. In one family, with the complete phenotype, a novel splice site mutation in exon 15 (1599 +1 G to A) is described. No mutations in the EYA1 gene were found in a second family presenting with ear pits, deafness, and renal anomalies, but lacking branchial fistulae. These and other findings from the literature suggest the existence of genetic heterogeneity of the BOR, BO, and other related phenotypes, with two or more genes involved.