GENETIC-LINKAGE OF THE MARFAN-SYNDROME, ECTOPIA LENTIS, AND CONGENITAL CONTRACTURAL ARACHNODACTYLY TO THE FIBRILLIN GENES ON CHROMOSOME-15 AND CHROMOSOME-5
GENETIC-LINKAGE OF THE MARFAN-SYNDROME, ECTOPIA LENTIS, AND CONGENITAL CONTRACTURAL ARACHNODACTYLY TO THE FIBRILLIN GENES ON CHROMOSOME-15 AND CHROMOSOME-5
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DOI：
10.1056/nejm199204023261401
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发表时间：
1992-04-02
影响因子：
158.5
通讯作者：
RAMIREZ, F
中科院分区：
文献类型：
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作者：
TSIPOURAS, P;DELMASTRO, R;RAMIREZ, F
背景。大糖蛋白原纤维蛋白是许多组织中含有弹性蛋白的微原纤维的结构成分。马凡综合征与 15 号染色体上的原纤维蛋白基因有关，但先天性挛缩性蜘蛛指畸形（具有该综合征的一些身体特征）与 5 号染色体上的原纤维蛋白基因有关。方法。使用原纤维蛋白基因的特定标记，我们对 28 个马凡综合征家系和 8 个患有四种表型相关疾病的家系进行了遗传连锁分析 - 先天性挛缩性蜘蛛指畸形（3 个家系）、晶状体异位 (2)、二尖瓣脱垂综合征 (2) 和主动脉环扩张 (1)。结果。马凡综合征仅与 15 号染色体上的原纤维蛋白基因之间建立了遗传连锁，最大 Lod 得分为 25.6（连锁几率为 10(25-6):1）。异位晶状体也与 15 号染色体上的原纤维蛋白基因相关，而先天性挛缩性蜘蛛指畸形则与 5 号染色体上的原纤维蛋白基因相关。二尖瓣脱垂与 5 号染色体上的原纤维蛋白基因没有关联； 15 号染色体的研究没有提供任何信息。主动脉环扩张与原纤维蛋白基因均无关。结论。马凡氏综合症似乎是由 15 号染色体上的单个原纤维蛋白基因突变引起的。通过遗传连锁和分析来诊断马凡氏综合症现在在许多家庭中是可行的。
Background. The large glycoprotein fibrillin is a structural component of elastin-containing microfibrils found in many tissues. The Marfan syndrome has been linked to the fibrillin gene on chromosome 15, but congenital contractural arachnodactyly, which shares some of the physical features of the syndrome, has been linked to the fibrillin gene on chromosome 5.Methods. Using specific markers for the fibrillin genes, we performed genetic linkage analysis in 28 families with the Marfan syndrome and 8 families with four phenotypically related disorders - congenital contractural arachnodactyly (3 families), ectopia lentis (2), mitral-valve prolapse syndrome (2), and annuloaortic ectasia (1).Results. Genetic linkage was established between the Marfan syndrome and only the fibrillin gene on chromosome 15, with a maximum lod score of 25.6 (odds for linkage, 10(25-6):1). Ectopia lentis was also linked to the fibrillin gene on chromosome 15, whereas congenital contractural arachnodactyly was linked to the fibrillin gene on chromosome 5. There was no linkage of mitral-valve prolapse to the fibrillin gene on chromosome 5; studies of chromosome 15 were not informative. Annuloaortic ectasia was not linked to either fibrillin gene.Conclusions. The Marfan syndrome appears to be caused by mutations in a single fibrillin gene on chromosome 15. Diagnosis of the Marfan syndrome by genetic linkage and analysis is now feasible in many families.