Homozygous null mutation in ODZ3 causes microphthalmia in humans

Purpose: Microphthalmia is a condition in which eyes are small in size, often associated with coloboma, as a result of aberrant eye development. Isolated microphthalmia is a model disease for studying early development of the human eye, and mutations in several key genes related to eye development have been linked to this phenotype. Methods: In our search for novel genes that cause autosomal recessive microphthalmia when mutated, we enrolled a family that consists of third-cousin parents and two children with isolated colobomatous microphthalmia. Results: Exome and autozygome analysis identified a null mutation in ODZ3, one of four vertebrate orthologs of odz in Drosophila. Conclusion: Our data highlight a role for ODZ3 in the early development of the human eye.