天津医药

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一个Fibrillin-1基因的新突变引起了严重的家族性马凡综合征

赵丰1,赵晨2,姜楠3,张秀梅4,Catharina Larsson5   

  1. 1. 天津胸科医院
    2. 南京医科大学第一临床医学院
    3. 天津医科大学附属天津胸科医院
    4. 河南省焦作市卫生学校
    5. CMM L8:01, Karolinska Institute, Stockholm, Sweden
  • 收稿日期:2011-11-21 修回日期:2012-02-14 出版日期:2012-06-15 发布日期:2012-06-15
  • 通讯作者: 赵晨

A Novel Mutation of Fibrillin-1 Gene Caused Serve Phenotypes of Familial Marfan Syndrome

  • Received:2011-11-21 Revised:2012-02-14 Published:2012-06-15 Online:2012-06-15

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摘要： 摘要 目的：马凡综合征是一种常染色体显性遗传疾病，它的典型临床表现常常累及心血管系统，眼部和骨骼系统。目前，已经有两个致病基因被报道，包括Fibrillin-1 (FBN1) and TGFBR2 基因。本研究目的是为了探索一个中国常染色体显性遗传的马凡氏综合征家系的遗传致病基因。方法：我们对此家系中全部患者临床表型进行了完整的分析记录，对加息全部参与者的DNA进行了排除连锁定位和FBN1基因的直接测序研究。结果：连锁分析在此家系中排除了TGFBR2位点，而将此家系连锁到位于15q21.1区的FBN1基因附件的位点。直接测序结果显示此家系中存在一个新的FBN1基因的提前终止密码子突变（PTC）。结论：这个严重的突变与此家系中的严重临床表现，特别是心血管畸形相关。

关键词: 纤原蛋白-1, 连锁分析, 马凡氏综合征, 基因突变

Abstract: Abstract Objiective: Marfan syndrome (MFS), an autosomal dominant inherited disease, has variable clinical manifestations typically affecting the cardiovascular, ocular and skeletal systems. Two causative genes for MFS have been demonstrated so far: Fibrillin-1 (FBN1) and TGFBR2 gene. This study aims to indentify the disease causing gene in a Chinese family with autosomal dominant MFS. Method:The detailed clinical examinations were performed and documented on each patient.DNA samples were collected from all participants.Exclusive mapping and mutation screening of FBN1 gene by direct sequencing were carried out. Results:After exclusion of the TGFBR2 locus by linkage analysis, significant linkage was found with markers of the FBN1 locus in the 15q21.1 region in both families. We then identified a novel mutation of FBN1,which is a premature termination codon (PTC) mutation. Conclusion:This server mutation correlates with the server phenotype, specifically the cardiovascular malformation, in the family.

Key words: Fibrillin-1, Linkage analysis, Marfan Syndrome, Mutation