Milewicz D M
Department of Internal Medicine, University of Texas-Houston Medical School 77030, USA.
Curr Opin Cardiol. 1998 May;13(3):198-204.
Two inherited disorders of connective tissue have major cardiovascular complications, Marfan syndrome and Ehlers-Danlos syndrome type IV. Major progress has been made toward understanding both the genetic defect and the molecular pathogenesis of these two disorders. Marfan syndrome results from mutations in the FBN1 gene, which encodes fibrillin-1, an extracellular matrix component found in structures called microfibrils. Histologic characterization of the effect of FBN1 mutations on fibrillin-1 cellular processing and microfibril formation has provided insights into fibrillin-1 function. Ehlers-Danlos syndrome type IV results from mutations in the COL3A1 gene, which encodes the polypeptides in type III collagen. Despite advances in the molecular genetics of these two disorders, there is not a molecular diagnostic test for these syndromes based on the identification of gene mutations. Marfan syndrome remains primarily a clinical diagnosis. Biochemical analysis of the amount of type III collagen produced by dermal fibroblasts has proven to be a powerful diagnostic test for Ehlers-Danlos syndrome type IV.
两种遗传性结缔组织疾病有主要的心血管并发症，即马方综合征和IV型埃勒斯-当洛综合征。在了解这两种疾病的基因缺陷和分子发病机制方面已经取得了重大进展。马方综合征是由FBN1基因突变引起的，该基因编码原纤蛋白-1，这是一种在称为微原纤维的结构中发现的细胞外基质成分。对FBN1突变对原纤蛋白-1细胞加工和微原纤维形成的影响进行组织学特征分析，有助于深入了解原纤蛋白-1的功能。IV型埃勒斯-当洛综合征是由COL3A1基因突变引起的，该基因编码III型胶原蛋白中的多肽。尽管这两种疾病的分子遗传学有了进展，但基于基因突变鉴定的针对这些综合征的分子诊断测试尚未出现。马方综合征仍然主要是临床诊断。对真皮成纤维细胞产生的III型胶原蛋白量进行生化分析，已被证明是诊断IV型埃勒斯-当洛综合征的有力测试方法。
