Price J A, Bowden D W, Wright J T, Pettenati M J, Hart T C
Department of Biochemistry, Wake Forest University School of Medicine, Bowman Gray Campus, Winston-Salem, NC 27157, USA.
Hum Mol Genet. 1998 Mar;7(3):563-9. doi: 10.1093/hmg/7.3.563.
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.
毛发-牙齿-骨综合征（TDO）是一种常染色体显性疾病，其特征为毛发、牙齿和骨骼异常。TDO的主要临床表现包括牛牙症、牙釉质发育不全、出生时头发卷曲以及颅骨厚度和密度增加。这些多效性临床特征提示了一个调控上皮-间充质相互作用的发育基因的作用。我们最近将TDO基因座定位到17号染色体q21区，该区域包含远端缺失同源框基因家族的两个成员，即DLX3和DLX7。在本文中，我们描述了人类DLX3和DLX7的基因组克隆和测序，并鉴定出人类DLX3中的一个4bp缺失，该缺失与六个家系中的TDO表型相关。观察到的突变预计会导致移码和过早终止密码子，从而导致功能改变的DLX3。DLX基因中人类突变的这一首次报道与小鼠研究一致，表明它们在毛发、牙齿和骨骼发育中起重要作用。
