Katzke Stefanie, Booms Patrick, Tiecke Frank, Palz Monika, Pletschacher Angelika, Türkmen Seval, Neumann Luitgard M, Pregla Reinhard, Leitner Christa, Schramm Cornelia, Lorenz Peter, Hagemeier Christian, Fuchs Josefine, Skovby Flemming, Rosenberg Thomas, Robinson Peter N
Institute of Medical Genetics, Charité University Hospital, Berlin, Germany.
Hum Mutat. 2002 Sep;20(3):197-208. doi: 10.1002/humu.10112.
Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome (MFS), an autosomal dominant heritable disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. FBN1 mutations have also been identified in a series of related disorders of connective tissue collectively termed type-1 fibrillinopathies. We have developed temperature-gradient gel electrophoresis (TGGE) assays for all 65 FBN1 exons, screened 126 individuals with MFS, other type-1 fibrillinopathies, and other potentially related disorders of connective tissue for FBN1 mutations, and identified a total of 53 mutations, of which 33 are described here for the first time. Several mutations were identified in individuals with fibrillinopathies other than classic Marfan syndrome, including aneurysm of the ascending aorta with only minor skeletal anomalies, and several individuals with only skeletal and ocular involvement. The mutation detection rate in this study was 42% overall, but was only 12% in individuals not fulfilling the diagnostic criteria for MFS, suggesting that clinical overdiagnosis is one reason for the low detection rate observed for FBN1 mutation analysis.
原纤蛋白-1（FBN1）基因的突变会导致马凡综合征（MFS），这是一种常染色体显性遗传的结缔组织疾病，在骨骼、眼部和心血管系统有显著表现。FBN1突变也在一系列统称为1型原纤蛋白病的相关结缔组织疾病中被发现。我们针对FBN1的所有65个外显子开发了温度梯度凝胶电泳（TGGE）检测方法，对126名患有马凡综合征、其他1型原纤蛋白病以及其他潜在相关结缔组织疾病的个体进行FBN1突变筛查，共鉴定出53个突变，其中33个在此首次描述。在非典型马凡综合征的原纤蛋白病个体中发现了几个突变，包括仅伴有轻微骨骼异常的升主动脉瘤，以及几名仅有骨骼和眼部受累的个体。本研究中的突变检出率总体为42%，但在不符合马凡综合征诊断标准的个体中仅为12%，这表明临床过度诊断是FBN1突变分析检出率低的一个原因。
