Milewicz D M
Department of Internal Medicine, University of Texas Medical School, Houston 77030.
Tex Heart Inst J. 1994;21(1):22-9.
The Marfan syndrome is an autosomal dominant disorder with pleiotropic manifestations that involve the cardiovascular, ocular, and skeletal systems. Through a number of investigational approaches, the gene encoding for fibrillin, the FBN1 gene on chromosome 15, has been identified as the defective gene causing the Marfan syndrome. Fibrillin is the large glycoprotein with a repetitive domain structure and is a major protein component of microfibrils, a fibrillar system closely associated with elastin in connective tissue. Mutational analysis of defects in the FBN1 gene in patients with the Marfan syndrome has revealed that most mutations are private or unique in an affected individual or family. Analysis of fibrillin protein or gene defects in individuals with related phenotypes has revealed that a perinatal lethal syndrome, termed neonatal Marfan syndrome, is due to FBN1 gene mutations. In addition, fibroblast cell strains from a subset of patients with idiopathic scoliosis have fibrillin protein defects. Last, fibroblasts from calves affected with bovine Marfan syndrome display defects in the fibrillin protein. These studies have wide-ranging implications in the diagnosis, treatment, and prevention of Marfan syndrome and related disorders.
马凡综合征是一种常染色体显性疾病，具有多效性表现，累及心血管、眼和骨骼系统。通过多种研究方法，已确定位于15号染色体上的原纤维蛋白编码基因FBN1基因是导致马凡综合征的缺陷基因。原纤维蛋白是一种具有重复结构域的大型糖蛋白，是微原纤维的主要蛋白质成分，微原纤维是一种与结缔组织中的弹性蛋白密切相关的纤维系统。对马凡综合征患者FBN1基因缺陷的突变分析表明，大多数突变在受影响的个体或家族中是私有的或独特的。对具有相关表型的个体进行原纤维蛋白或基因缺陷分析表明，一种围产期致死综合征，即新生儿马凡综合征，是由FBN1基因突变引起的。此外，一部分特发性脊柱侧凸患者的成纤维细胞系存在原纤维蛋白缺陷。最后，患牛马凡综合征的小牛的成纤维细胞显示出原纤维蛋白缺陷。这些研究对马凡综合征及相关疾病的诊断、治疗和预防具有广泛的意义。
