[HOX genes and the limb development in the clinical praxis and in the experiment]

In human, congenital malformations of the limbs are ranked among the most prevalent of all congenital birth defects. Substantial portion of these defects has genetic origin. Increasing knowledge about the particular mutations responsible for limb malformations in human results in the increasing availability of DNA diagnostic procedures for confirmation of clinical diagnosis and family counselling. Increasing understanding of the underlying developmental processes revealed by studying limb defects both in human and animal models may offer better therapeutic options in the future. This review concentrates on the role of Hox genes in limb development. Man, as well as other mammals, has 39 HOX genes, divided into 4 complexes (clusters). HOX genes play a major role in body plan layout and development of many organ systems. Experimental data show that during the limb development, HOX genes influence patterning along the proximodistal and anteroposterior (thumb-little finger) axis of the limb bud. In human, limb malformation was described in patients with mutations in HOXA11, HOXA13, HOXD10, and HOXD13 genes. Most frequent among these malformations are hand-foot-genital syndrome caused by HOXA13 gene mutation, and synpolydactyly caused by HOXD13 mutation. Severity of the phenotype manifestation of these diseases is variable, and depends on the particular mutation type, where point mutations, polyalanine expansions and deletions can take part.