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.