Mutation of PAX2 in two siblings with renal-coloboma syndrome

PAX2 is a member of a multigene family containing a paired box domain that was initially identified in Drosophila and subsequently in vertebrates (1). PAX genes play a critical role in embryogenesis, as demonstrated by mouse mutants and fetal expression patterns (2). Mutations causing autosomal dominant syndromes in humans have been documented in three of the nine PAX genes. Mutations in PAX3 cause Waardenburg syndrome types I and III (3,4); mutations in PAX6 cause aniridia (5-7) and recently we have shown that PAX2 is mutated in a family with autosomal dominant optic nerve coloboma, renal anomalies and vesicoureteric reflux (8). The disease phenotype associated with PAX2 mutations in humans may show variability. Indeed, there have been no other reports of a syndrome in humans with exactly the same phenotype as the family in which the PAX2 mutation was