Identification of a novel heterozygous mutation in the DLX 3 gene of a Chinese family with tricho-dento-ossenous syndrome

Tricho-dento-ossenous (TDO) syndrome is a rare autosomal dominant disorder, characterized by abnormal hair, teeth and bone. Previous studies have shown that TDO syndrome is associated with the DLX3 homeobox gene mutation, a transcriptional activator regulating target gene expression by binding to cognate DNA sequences. In this study, we reported a five-generation Chinese family with typically features of TDO syndrome. The affected family members have presented with thin or fine hair, sparse or even absent eyebrows and eyelashes and markedly congenitally missing teeth. To investigate the potential involvement of disease-related gene mutation in the development of TDO syndrome in this family, we analyzed the genomic DNA sequences of family member blood samples by PCR amplification and Sanger sequencing, and mapped the disease locus of this identified family to human chromosome 17q21 and found a novel heterozygous mutation in exon 3 of DLX3. This guanine to cytosine transversion at nucleotide position 534 (c.534 G > C) in DLX3 gene leads to a glutamine to histidine substitution of amino acid 178 (p.Gln178His), a severe missense mutation in the primary sequence of DLX3 protein. Our results suggest that defective DLX3 expression caused by multiple genomic mutations functions as the principal pathogenic mechanism mediating the development of TDO syndrome.