DLX3 c-561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome
DLX3 c-561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome
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DOI：
10.1002/ajmg.a.32132
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发表时间：
2008-02-01
影响因子：
2
通讯作者：
Luder, Hans U.
中科院分区：
文献类型：
--
作者：
Wright, J. Timothy;Hong, Sung P.;Luder, Hans U.
无远端同源盒基因DLX3在多种组织中表达，包括胎盘、皮肤、头发、牙齿和骨骼。DLX3基因（c.571_574delGGGG）突变导致毛牙骨综合征（TDO），其特征是毛发、牙齿和骨骼异常。对分离DLX3 c.561_562delCT突变的亲属的评估显示，与DLX3 c. 571_574delgggg突变一样，头发、牙齿和骨骼发生了明显的变化。先前，DLX3 c.561_562delCT突变与常染色体显性无染色体发育不全伴牛牙畸形有关。本研究表明，与具有DLX3 c-571_574delGGGG突变的个体相比，DLX3 c-560_561delCT突变导致TDO表型减弱，头发，牙齿和骨骼表现不那么严重。对DLX3等位基因突变个体的仔细表型分析显示，表型严重程度存在显著差异，这表明DLX3蛋白的羧基端在这些不同组织的发育过程中决定其功能至关重要。(C) 2008 Wiley-Liss, Inc。
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. (C) 2008 Wiley-Liss, Inc.