Snajdr Pavel, Grim Milos, Liska Frantisek
Univerzita Karlova v Praze, 1. lékarská fakulta, Anatomický ústav.
Cas Lek Cesk. 2010;149(1):4-9.
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.
在人类中，肢体先天性畸形位列所有先天性出生缺陷中最为常见的类型。这些缺陷中有很大一部分源于遗传。随着人们对导致人类肢体畸形的特定突变的了解不断增加，用于确诊临床诊断和进行遗传咨询的DNA诊断程序也越来越多。通过研究人类和动物模型中的肢体缺陷所揭示的对潜在发育过程的深入理解，可能会在未来提供更好的治疗选择。本综述着重探讨Hox基因在肢体发育中的作用。人类以及其他哺乳动物拥有39个HOX基因，分为4个复合体（簇）。HOX基因在身体蓝图布局和许多器官系统的发育中发挥着重要作用。实验数据表明，在肢体发育过程中，HOX基因会影响沿肢体芽近端-远端和前后（拇指-小指）轴的模式形成。在人类中，已在HOXA11、HOXA13、HOXD10和HOXD13基因突变的患者中发现了肢体畸形。这些畸形中最常见的是由HOXA13基因突变引起的手足生殖器综合征，以及由HOXD13突变引起的并指多指畸形。这些疾病的表型表现严重程度各不相同，取决于特定的突变类型，其中点突变、多聚丙氨酸扩增和缺失都可能参与其中。
