Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms.
Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms.
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DOI：
10.1172/jci116490
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发表时间：
1993-06
期刊：
影响因子：
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通讯作者：
G. Tromp;Yuli Wu;D. Prockop;S. Madhatheri;Caren Kleinert;J. Earley;J. Zhuang;Ö. Norrgård;Darling Rc;W. Abbott
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文献类型：
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作者：
G. Tromp;Yuli Wu;D. Prockop;S. Madhatheri;Caren Kleinert;J. Earley;J. Zhuang;Ö. Norrgård;Darling Rc;W. Abbott
对54例主动脉瘤患者的III型前胶原基因的三螺旋结构域进行了详细的DNA测序。43名男性和11名女性患者来自50个不同的家庭和5个不同的民族。43名患者至少有一名额外的血亲患有动脉瘤。用28个特异性测序引物对5个重叠的不对称聚合酶链式反应产物进行测序，这些产物覆盖了III型前胶原蛋白三螺旋结构域的全部编码序列。对测序凝胶的分析显示，只有两个核苷酸变化改变了蛋白质的结构。一种是用苏氨酸取代501位氨基酸上的Pro，其功能重要性尚未明确。另一种是用精氨酸取代第136位必需的甘氨酸。在54名患者中，有40名患者的信使核糖核酸多态检测证实两个等位基因都有表达。结果表明，III型前胶原基因突变只是大约2%的主动脉瘤的原因。
Detailed DNA sequencing of the triple-helical domain of type III procollagen was carried out on cDNA prepared from 54 patients with aortic aneurysms. The 43 male and 11 female patients originated from 50 different families and five different nationalities. 43 patients had at least one additional blood relative who had aneurysms. Five overlapping asymmetric PCR products, covering all the coding sequences of the triple-helical domain of type III procollagen, were sequenced with 28 specific sequencing primers. Analysis of the sequencing gels revealed only two nucleotide changes that altered the structure of the protein. One was a substitution of threonine for proline at amino acid position 501 and its functional importance was not clearly established. The other was a substitution of arginine for an obligatory glycine at amino acid position 136. In 40 of the 54 patients, detection of a polymorphism in the mRNA established that both alleles were expressed. The results indicate that mutations in type III procollagen are the cause of only about 2% of aortic aneurysms.