Mundlos S
Institute for Medical Genetics, Charité, Universitätsmedizin Berlin, Berlin, Germany.
Clin Genet. 2009 Aug;76(2):123-36. doi: 10.1111/j.1399-0004.2009.01238.x.
Brachydactyly refers to shortening of the hands and/or feet due to missing, deformed, or shortened bones. It may occur as an isolated trait or as part of a syndrome. According to their pattern of skeletal involvement, the isolated brachydactyly forms have been categorized in the groups A-D including several subgroups. As in many other genetic conditions, there is considerable phenotypic overlap between the groups. The identification of the molecular causes of these conditions has offered insights into their pathogenesis. The generation of animal models has facilitated research on the pathogenic events during digit development that lead to the brachydactyly phenotype. These studies have shown that the BMP pathway plays a pivotal role in the normal development of digits and joints and that the majority of brachydactyly disease genes are directly or indirectly linked to this pathway. Together, these genes function in a regulatory network which is deregulated in the disease state. As a consequence of the close interactions within the network, overlapping phenotypes are generated that are, nevertheless, characterized by specific recognizable patterns. This principle does not only apply for the brachydactylies but is also valid for many other disease entities. Groups of diseases that show a common phenotypic pattern due to the deregulation of a molecular network are suggested to be called molecular disease families.
短指（趾）症是指由于骨骼缺失、畸形或缩短导致的手和/或脚的缩短。它可能作为一种孤立的性状出现，也可能是综合征的一部分。根据骨骼受累的模式，孤立性短指（趾）症的类型已被分为A - D组，包括几个亚组。与许多其他遗传疾病一样，这些组之间存在相当大的表型重叠。对这些疾病分子病因的鉴定为其发病机制提供了见解。动物模型的建立促进了对导致短指（趾）症表型的指（趾）发育过程中致病事件的研究。这些研究表明，骨形态发生蛋白（BMP）通路在指（趾）和关节的正常发育中起关键作用，并且大多数短指（趾）症疾病基因直接或间接与该通路相关。这些基因共同作用于一个调控网络，该网络在疾病状态下失调。由于网络内的紧密相互作用，产生了重叠的表型，然而，这些表型具有特定的可识别模式。这一原则不仅适用于短指（趾）症，也适用于许多其他疾病实体。由于分子网络失调而表现出共同表型模式的疾病组被建议称为分子疾病家族。
