Sakai Lynn Y, Keene Douglas R, Renard Marjolijn, De Backer Julie
Departments of Molecular & Medical Genetics and Biochemistry & Molecular Biology, Oregon Health & Science University and Shriners Hospital for Children, 3101 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Biomedical Engineering, Oregon Health & Science University and Shriners Hospital for Children, 3101 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Gene. 2016 Oct 10;591(1):279-291. doi: 10.1016/j.gene.2016.07.033. Epub 2016 Jul 18.
FBN1 encodes the gene for fibrillin-1, a structural macromolecule that polymerizes into microfibrils. Fibrillin microfibrils are morphologically distinctive fibrils, present in all connective tissues and assembled into tissue-specific architectural frameworks. FBN1 is the causative gene for Marfan syndrome, an inherited disorder of connective tissue whose major features include tall stature and arachnodactyly, ectopia lentis, and thoracic aortic aneurysm and dissection. More than one thousand individual mutations in FBN1 are associated with Marfan syndrome, making genotype-phenotype correlations difficult. Moreover, mutations in specific regions of FBN1 can result in the opposite features of short stature and brachydactyly characteristic of Weill-Marchesani syndrome and other acromelic dysplasias. How can mutations in one molecule result in disparate clinical syndromes? Current concepts of the fibrillinopathies require an appreciation of tissue-specific fibrillin microfibril microenvironments and the collaborative relationship between the structures of fibrillin microfibril networks and biological functions such as regulation of growth factor signaling.
FBN1基因编码原纤蛋白-1，这是一种聚合形成微原纤维的结构大分子。原纤蛋白微原纤维是形态独特的原纤维，存在于所有结缔组织中，并组装成组织特异性的结构框架。FBN1是马凡综合征的致病基因，马凡综合征是一种遗传性结缔组织疾病，其主要特征包括身材高大、蜘蛛指、晶状体异位以及胸主动脉瘤和夹层。FBN1基因中有一千多个个体突变与马凡综合征相关，这使得基因型与表型之间的关联变得困难。此外，FBN1特定区域的突变可导致身材矮小和短指等相反特征，这些特征是Weill-Marchesani综合征和其他肢端发育异常的典型表现。一个分子中的突变怎么会导致不同的临床综合征呢？目前关于原纤蛋白病的概念需要了解组织特异性的原纤蛋白微原纤维微环境以及原纤蛋白微原纤维网络结构与生物功能（如生长因子信号调节）之间的协作关系。
