Classic, atypically severe and neonatal Marfan syndrome:: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40
Classic, atypically severe and neonatal Marfan syndrome:: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40
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DOI：
10.1038/sj.ejhg.5200582
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发表时间：
2001-01-01
影响因子：
5.2
通讯作者：
Rosenberg, T
中科院分区：
文献类型：
--
作者：
Tiecke, F;Katzke, S;Rosenberg, T
马凡氏综合征是一种常染色体显性遗传的结缔组织疾病，主要表现在骨骼、眼部和心血管系统。在马凡氏综合征家族内和家族间以及FBN 1突变引起的结缔组织相关疾病（统称为1型原纤维蛋白病）的个体中，存在显著程度的临床变异性。FBN 1外显子24-32中所谓的新生儿区域包括迄今为止描述的少数几个普遍接受的基因型-表型相关性之一。在这项工作中，我们报告了12 FBN 1突变确定的温度梯度凝胶电泳筛选外显子24-40在127人与马凡氏综合征或相关疾病。这里报告的数据，以及其他已发表的报告，记录了外显子24-32的突变的显着聚类。尽管所有报道的与新生儿马凡氏综合征相关的突变和大多数与严重疾病相关的点突变都发现于外显子24-32，但与经典马凡氏综合征相关的突变也发生在该区域。无法预测外显子24-32中的特定突变是否与经典型、重症或新生儿马凡氏综合征相关。
Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, an autosomal dominant disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. There is a remarkable degree of clinical variability both within and between families with Marfan syndrome as well as in individuals with related disorders of connective tissue caused by FBN1 mutations and collectively termed type-1 fibrillinopathies. The so-called neonatal region in FBN1 exons 24-32 comprises one of the few generally accepted genotype-phenotype correlations described to date. In this work, we report 12 FBN1 mutations identified by temperature-gradient gel electrophoresis screening of exons 24-40 in 127 individuals with Marfan syndrome or related disorders. The data reported here, together with other published reports, document a significant clustering of mutations in exons 24-32. Although all reported mutations associated with neonatal Marfan syndrome and the majority of point mutations associated with atypically severe presentations have been found in exons 24-32 mutations associated with classic Marfan syndrome occur in this region as well. It is not possible to predict whether a given mutation in exons 24-32 will be associated with classic, atypically severe, or neonatal Marfan syndrome.