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

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder charact erized by the association of branchial cysts or fistulae, external ear malf ormation and/or preauricular pits, hearing loss, and renal anomalies. Mutat ions in the EYA1 gene, a human homologue of the Drosophila 'eyes absent' ge ne, have been identified as cause of the syndrome. We report here two famil ies 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, d eafness, and renal anomalies, but lacking branchial fistulae. These and oth er findings from the literature suggest the existence of genetic heterogene ity of the BOR, BO, and other related phenotypes, with two or more genes in volved.