遗传性结缔组织病发生后通常会累及人全身各个系统,该类疾病的发生与构成结缔组织的纤维蛋白基因发生突变引起的蛋白异构有关。原纤维蛋白-2 (fibrillin-2, FBN2)是微纤维重要组成部分,参与全身结缔组织中弹性纤维的形成。FBN2基因突变与遗传性结缔组织病,如先天性挛缩性蜘蛛指样症(congenital contractural arachnodactyly, CCA),黄斑变性(macular degeneration, MD),肌病等密切相关。研究发现FBN2基因是目前唯一已知的CCA致病基因,且不同位点的突变与CCA患者一系列临床表症的关系密切。该基因也是MD的致病基因,是肌病的风险基因,并与其他结缔组织病的发生有关。本文对FBN2基因突变引起的CCA、黄斑变性以及肌病等其他遗传性结缔组织病的临床表症及相关研究进展进行了综述,以期为深入探究FBN2基因突变致病的具体分子机制提供基础,为研究针对FBN2基因突变造成的难治性疾病的治疗药物提供理论依据。

Fibrillin-2 (FBN2) is an important component of microfibers which are involved in the formation of elastic fibers in connective tissue throughout the human body. Hereditary connective tissue diseases may result from genetic mutations of FBN2 causing heterogeneity of fibrin. Genetic mutations of FBN2 are associated with a variety of hereditary connective tissue diseases including Congenital Contractural Arachnodactyl (CCA), Macular Degeneration (MD), and myopathy. Studies have shown that the FBN2 gene is recognized as the only pathogenic gene related to CCA and that CCA patients have different clinical presentations depending on the identified genetic mutations at different FBN2 sites. In this review, we summarize the roles of FBN2, its mutations and impact on the physiological and pathological processes of many hereditary connective tissue diseases. We include brief descriptions of clinical manifestations of these diseases providing a basis for further exploration of the specific molecular mechanism of FBN2 gene mutation pathogenesis which provides a theoretical basis for the therapy and medications for refractory diseases caused by FBN2 gene mutation.