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.

Authors

Gerard Tromp, Thomas Jefferson UniversityFollow
Yuli Wu, Thomas Jefferson University
Darwin J. Prockop, Thomas Jefferson UniversityFollow
Swarna L. Madhatheri, Thomas Jefferson University
Caren Kleinert, Thomas Jefferson University
James J. Earley, Thomas Jefferson UniversityFollow
Jiapiao Zhuang, Thomas Jefferson University
Orjan Norrgård, University of Umeå
R. Clement Darling, Harvard Medical School
William M. Abbott, Harvard Medical School
C. William Cole, University of Ottawa
Pekka Jaakkola, University of Kuopio
Markku Ryynanen, University of Kuopio
William H. Pearce, NW University Medical School
James S.T. Yao, NW University Medical School
Kari Majamaa, University of Oulu
Stanton N. Smullens, Thomas Jefferson UniversityFollow
Zoran Gatalica, Thomas Jefferson UniversityFollow
Robert E. Ferrell, University of Pittsburgh
Sergio A. Jimenez, Thomas Jefferson UniversityFollow
Charles E. Jackson, Henry Ford Hospital
Virginia V. Michels, Mayo Clinic
Michael Kaye, Montreal General Hospital
Helena Kuivaniemi, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

6-1-1993

Comments

This article has been peer reviewed. It is the author’s final published version in Journal of Clinical Investigation

Volume 91, Issue 6, June 1993, Pages 2539-2545

The published version is available at DOI: 10.1172/JCI116490. Copyright © The American Society for Clinical Investigation, Inc.

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.

Recommended Citation

Tromp, Gerard; Wu, Yuli; Prockop, Darwin J.; Madhatheri, Swarna L.; Kleinert, Caren; Earley, James J.; Zhuang, Jiapiao; Norrgård, Orjan; Darling, R. Clement; Abbott, William M.; Cole, C. William; Jaakkola, Pekka; Ryynanen, Markku; Pearce, William H.; Yao, James S.T.; Majamaa, Kari; Smullens, Stanton N.; Gatalica, Zoran; Ferrell, Robert E.; Jimenez, Sergio A.; Jackson, Charles E.; Michels, Virginia V.; Kaye, Michael; and Kuivaniemi, Helena, "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." (1993). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 113.
https://jdc.jefferson.edu/bmpfp/113

PubMed ID

8514866