DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome.

The distal-less homeobox gene DLX3 is expressed in a variety of tissues including placenta, skin, hair, teeth, and bone. Mutation of DLX3 (c.571_574delGGGG) causes the tricho-dento-osseous syndrome (TDO), characterized by abnormal hair, teeth, and bone. Evaluation of a kindred segregating the DLX3 c.561_562delCT mutation revealed distinct changes in the hair, teeth, and bones as has been observed with the DLX3 c.571_574delGGGG mutation. Previously, the DLX3 c.561_562delCT mutation was associated with autosomal dominant amelogenesis imperfecta with taurodontism. The present study shows that the DLX3 c.560_561delCT mutation causes an attenuated TDO phenotype with less severe hair, tooth, and bone manifestations compared with individuals having the DLX3 c.571_574delGGGG mutation. Careful phenotyping of individuals with allelic DLX3 mutations reveals marked differences in phenotypic severity indicating that the carboxy-terminus of the DLX3 protein is critical in determining its function during development in these different tissues.