Spitz François, Montavon Thomas, Monso-Hinard Christine, Morris Michael, Ventruto Maria-Luisa, Antonarakis Stylianos, Ventruto Valerio, Duboule Denis
Department of Zoology and Animal Biology, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
Genomics. 2002 Apr;79(4):493-8. doi: 10.1006/geno.2002.6735.
Mesomelic dysplasia is a severe shortening of forearms and forelegs, and is found in several distinct human syndromes. Here, we report the cloning of the breakpoints of a human t(2;8)(q31;p21) balanced translocation associated with mesomelic dysplasia of the upper limbs, as well as with vertebral defects. We show that this translocation does not disrupt any gene, hence it most likely exerts its deleterious effect by modifying gene regulation. The HOXD complex lies approximately 60 kb from the translocation breakpoint on chromosome 2. This cluster of genes has an important role in the development of both the vertebral column and the limbs. Only a few cases of mutations of these homeotic genes have been described so far in humans. However, gain- and loss-of-function of Hoxd genes in mice can induce mesomelic dysplasia-like phenotypes, suggesting that misexpression of HOXD genes may indeed be at the origin of this hereditary phenotype.
中肢发育不全是指前臂和前腿严重缩短，在几种不同的人类综合征中都有发现。在此，我们报告了与上肢中肢发育不全以及脊椎缺陷相关的人类t(2;8)(q31;p21)平衡易位断点的克隆。我们发现这种易位并未破坏任何基因，因此它很可能是通过改变基因调控发挥其有害作用。HOXD基因簇位于2号染色体上距离易位断点约60 kb处。这一基因簇在脊柱和四肢的发育中都起着重要作用。到目前为止，人类中仅描述了少数这些同源异型基因的突变病例。然而，小鼠中Hoxd基因的功能获得和丧失可诱导中肢发育不全样表型，这表明HOXD基因的错误表达可能确实是这种遗传表型的根源。
