先天性马蹄内翻足致病基因的研究进展

Progress in the study on pathogenic genes of congenital clubfoot

先天性马蹄内翻足（congenital clubfoot，CCF）是一种常见的严重影响足的形态与功能的先天性畸形，占足部畸形的85％，发病率全世界约为1‰，男女比例约为2～2．5：1。中国人患病率为0．39‰，夏威夷人和毛利人为7‰，高加索人约为1．2‰，波利尼西亚人约为6．8‰，不同种族患病率不同。CCF患者同胞患病几率增加约30倍。两位同胞同时患病在单卵双生中的几率高达32．5％，而在双卵双生中仅为2．9％。上述研究表明CCF的发生与遗传因素密切相关，目前认为，CCF的发生是遗传因素与环境因素共同作用的结果，近年研究报道显示，CCF发病与几类相关基因的改变有着密切的联系。现就CCF致病基因研究进展综述如下。

Congenital clubfoot （CCF） is a common deformity of foot. Previous studies have shown that CCF is related to skeletal dysplasia, neuromuscular disease, soft tissue contractures, vascular anomalies, genetic factors and intrauterine growth retardation. However, more scholars believe that this disease is the result of the interactions of multiple genetic and environmental factors. The current study has found that the incidence of CCF is closely related to changes of some related genes. Hox genes are major genes in control of vertebrate embryonic development and organogenesis. Hox A and Hox D play an important role in regulating limb development. Hox genes have 4 basic functions during limb genesis： regulating the starting time of chondrocyte proliferation and differentiation and their speed; regulating the proliferation of undifferentiated mesenchymal cells; participating in the process of mesenchymal cell condensation to form the primordia of protoplasm; participating in the formation of chondrocytes. CCF correlates with the developmental abnormalities of bones, muscles, soft tissues, nerves, blood vessels and so on, and Hox genes regulate the formation of nerves, muscles, bones and blood vessels. It can be speculated from above functions of CCF and Hox genes that the occurrence of CCF is caused by abnormal regulation of Hox genes during limb development. The emergence of mutations in the diastrophic dysplasia sulfate transporter （DTDST） gene may cause damage to human growth and development, while DTDST gene mutations are not the only factors that cause CCF. Pituitary homeobox 1 （PITX1） gene is the main regulating gene in the lower limb development. It is involved in cell apoptosis through abelson tyrosine kinase （c-Abl） （nonreceptor tyrosine kinase）, and while cell apoptosis may be associated with the etiology of CCF. The research have showed that the alpha 1 chain of type IX collagen （COL9A1） gene may be the susceptibility gene for CCF. However, in which way COL9A1 gene participates in the process of CCF is still not clear. This article just reviewed the research progress of such pathogenic genes as Hox genes, DTDST gene, PITX1 gene, COL9A1 gene and so on.