Identification of a mutation in DLX3 associated with tricho-dento-osseous (TDO) syndrome

Tricho-dento-osseous syndrome (TDO) is an autosomal dominant disorder characterized by abnormal hair, teeth and bone. The main clinical manifestations of TDO include taurodontism, enamel hypoplasia, kinky, curly hair at birth and increased thickness and density of the cranial bones. These pleiotropic clinical features suggest the role of a developmental gene modulating epithelial-mesenchymal interactions. We recently mapped the TDO locus to chromosome 17q21, a region that includes two members of the distal-less homeobox gene family, DLX3 and DLX7. In this paper we describe genomic cloning and sequencing of both human DLX3 and DLX7 and identification of a 4 bp deletion in human DLX3 which correlates with the TDO phenotype in six families. The observed mutation is predicted to cause a frameshift and premature termination codon, resulting in a functionally altered DLX3. This first report of a human mutation in the DLX genes is consistent with murine studies indicating their important role in the development of hair, teeth and bone.