Putnam E A, Zhang H, Ramirez F, Milewicz D M
Department of Internal Medicine, University of Texas-Houston Medical School 77030, USA.
Nat Genet. 1995 Dec;11(4):456-8. doi: 10.1038/ng1295-456.
Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically similar to Marfan syndrome (MFS) and characterized by arachnodactyly, dolichostenomelia, scoliosis, multiple congenital contractures and abnormalities of the external ears. In contrast to MFS, CCA does not affect the aorta or the eyes. Two closely related genes, FBN1 located on chromosome 15q15-21.3 and FBN2 located at 5q23-31, encode large fibrillin proteins found in extracellular matrix structures called microfibrils. The MFS is caused by mutations in FBN1, while CCA has been genetically linked to FBN2 (refs 2, 5, 6). We now describe a pair of FBN2 missense mutations in two CCA patients that cause substitution of distinct cysteine residues in separate epidermal growth-factor-like (EGF) repeats. Our study provides final proof of the association between FBN2 mutations and CCA pathology, thus establishing the role of the fibrillin-2 in extracellular matrix physiology and pathology.
先天性挛缩性蜘蛛指（CCA）是一种常染色体显性疾病，其表型与马凡综合征（MFS）相似，特征为蜘蛛指、肢体细长、脊柱侧弯、多处先天性挛缩以及外耳异常。与MFS不同，CCA不影响主动脉或眼睛。两个密切相关的基因，位于15号染色体15q15 - 21.3的FBN1和位于5号染色体5q23 - 31的FBN2，编码在称为微原纤维的细胞外基质结构中发现的大型原纤蛋白。MFS由FBN1突变引起，而CCA在基因上与FBN2相关（参考文献2、5、6）。我们现在描述了两名CCA患者中的一对FBN2错义突变，这些突变导致在不同的表皮生长因子样（EGF）重复序列中不同半胱氨酸残基的替代。我们的研究为FBN2突变与CCA病理之间的关联提供了最终证据，从而确立了原纤蛋白-2在细胞外基质生理和病理中的作用。
