Tricho-dento-osseous syndrome and amelogenesis imperfecta with taurodontism are genetically distinct conditions

Amelogenesis imperfecta of the hypomaturation-hypoplasia type with taurodon tism (AIHHT) is inherited as a highly penetrant autosomal dominant trait. T hese dental findings are similar to those of another autosomal dominant con dition, the tricho-dento-osseous syndrome (TDO), from which AIHHT differs p rimarily by lack of changes in the hair and bones. TDO is characterized by a highly variable clinical phenotype. While enamel hypoplasia and taurodont ism appear to be present in all TDO cases, non-dental features may he absen t, with approximately half of TDO cases losing the kinky/curly hair phenoty pe seen in infancy by adolescence, and in almost 20% of cases, osseous chan ges are not evident. The genetic basis for AIHHT is unknown and it has been questioned whether AIHHT and TDO are separate conditions or a spectrum of disease. The genetic basis for TDO has recently been identified as a deleti on mutation in the distal-less 3 (DLX3) transcription factor gene. To deter mine if AIHHT and TDO represent variable expression of a common DLX3 gene m utation, allelic mutations of the DLX3 gene, or mutations in DLX7 (the link ed paralogue to DLX3 on chromosome 17), we have performed mutational analys is and sequencing studies of the DLX3 and DLX7 genes in three individuals ( two affected and one unaffected) from a family with AIHHT. Results of the a nalysis demonstrate that AIHHT and TDO are not due to a common DLX3 gene mu tation. Sequence analyses of the DLX3 and DLX7 genes suggest AIHHT is not d ue to genetic mutations or polymorphisms in the exons of these genes. These results suggest that AIHHT and TDO are two genetically distinct conditions .