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

Gerard Tromp, Yuli Wu, Darwin J. Prockop, Swarna L. Madhatheri, Caren Kleinert, James J. Earley, Jiapiao Zhuang, Örjan Norrgård, R. Clement Darling, William M. Abbott, C. William Cole, Pekka Jaakkola, Markku Ryynänen, William H. Pearce, James S T Yao, Kari Majamaa, Stanton N. Smullens, Zoran Gatalica, Robert E. Ferrell, Sergio A. JimenezCharles E. Jackson, Virginia V. Michels, Michael Kaye, Helena Kuivaniemi

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2539-2545
Number of pages7
JournalJournal of Clinical Investigation
Volume91
Issue number6
DOIs
StatePublished - 1993

Keywords

  • familial aneurysms
  • polymerase chain reaction
  • polymorphisms

ASJC Scopus subject areas

  • Medicine(all)

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