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Abstract：
Marfan syndrome is an inherited disorder of connective tissue manifested in the ocular, skeletal and cardiovascular systems. It is inherited as an autosomal dominant with high penetrance, but has great clinical variability. Linkage studies have mapped the Marfan locus to chromosome 15q15-21.3. There have been no reports of genetic heterogeneity in the syndrome. Following the identification of fibrillin (a glycoprotein component of the extracellular microfibril), immunohistopathological quantification of the protein in skin and fibroblast culture, and examination of fibrillin synthesis, extracellular transport, and incorporation into the extracellular matrix (D. M. Milewicz, R.E.P., E. S. Crawford and P. H. Byers, manuscript in preparation) have demonstrated abnormalities of fibrillin metabolism in most patients. A portion of the complementary DNA encoding fibrillin has been cloned and mapped by in situ hybridization to chromosome 15. Here we report that the fibrillin gene is linked to the Marfan phenotype (theta = 0.00; logarithm of the odds (lod) = 3.9) and describe a de novo missense mutation in the fibrillin gene in two patients with sporadic disease. We thus implicate fibrillin as the protein defective in patients with the Marfan syndrome.
摘要：
马凡氏综合征是一种表现在眼部的结缔组织遗传性疾病，骨骼和心血管系统。它作为常染色体显性遗传，具有高外显率，但有很大的临床变异性。连锁研究已将Marfan基因座定位到染色体15q15-21.3。目前尚无关于该综合征遗传异质性的报道。在鉴定纤丝蛋白（细胞外微纤丝的糖蛋白成分）之后，皮肤和成纤维细胞培养中蛋白质的免疫组织病理学定量，和原纤蛋白合成的检查，细胞外运输，并掺入细胞外基质(D.米莱维茨,R.E.P.,E·S·克劳福德和P·H·拜尔斯，准备中的手稿）已证明大多数患者的纤丝蛋白代谢异常。编码原纤维蛋白的互补DNA的一部分已被克隆并通过原位杂交定位到染色体15。在这里，我们报告了纤丝蛋白基因与Marfan表型相关（theta=0.00；赔率的对数（lod）=3.9），并描述了两名散发性疾病患者的纤丝蛋白基因中的从头错义突变。因此，我们暗示纤丝蛋白是马凡氏综合征患者的蛋白质缺陷。
