• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Jun 1993; 91(6): 2539–2545.
PMCID: PMC443315

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.


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Clifton MA. Familial abdominal aortic aneurysms. Br J Surg. 1977 Nov;64(11):765–766. [PubMed]
  • Tilson MD, Seashore MR. Human genetics of the abdominal aortic aneurysm. Surg Gynecol Obstet. 1984 Feb;158(2):129–132. [PubMed]
  • Tilson MD, Seashore MR. Fifty families with abdominal aortic aneurysms in two or more first-order relatives. Am J Surg. 1984 Apr;147(4):551–553. [PubMed]
  • Norrgård O, Rais O, Angquist KA. Familial occurrence of abdominal aortic aneurysms. Surgery. 1984 Jun;95(6):650–656. [PubMed]
  • Johansen K, Koepsell T. Familial tendency for abdominal aortic aneurysms. JAMA. 1986 Oct 10;256(14):1934–1936. [PubMed]
  • Powell JT, Greenhalgh RM. Multifactorial inheritance of abdominal aortic aneurysm. Eur J Vasc Surg. 1987 Feb;1(1):29–31. [PubMed]
  • Cole CW, Barber GG, Bouchard AG, McPhail NV, Roberge C, Waddell WG, Wellington JL. Abdominal aortic aneurysm: consequences of a positive family history. Can J Surg. 1989 Mar;32(2):117–120. [PubMed]
  • Darling RC, 3rd, Brewster DC, Darling RC, LaMuraglia GM, Moncure AC, Cambria RP, Abbott WM. Are familial abdominal aortic aneurysms different? J Vasc Surg. 1989 Jul;10(1):39–43. [PubMed]
  • Bengtsson H, Norrgård O, Angquist KA, Ekberg O, Oberg L, Bergqvist D. Ultrasonographic screening of the abdominal aorta among siblings of patients with abdominal aortic aneurysms. Br J Surg. 1989 Jun;76(6):589–591. [PubMed]
  • Webster MW, Ferrell RE, St Jean PL, Majumder PP, Fogel SR, Steed DL. Ultrasound screening of first-degree relatives of patients with an abdominal aortic aneurysm. J Vasc Surg. 1991 Jan;13(1):9–14. [PubMed]
  • Majumder PP, St Jean PL, Ferrell RE, Webster MW, Steed DL. On the inheritance of abdominal aortic aneurysm. Am J Hum Genet. 1991 Jan;48(1):164–170. [PMC free article] [PubMed]
  • Reilly JM, Tilson MD. Incidence and etiology of abdominal aortic aneurysms. Surg Clin North Am. 1989 Aug;69(4):705–711. [PubMed]
  • Lee B, Godfrey M, Vitale E, Hori H, Mattei MG, Sarfarazi M, Tsipouras P, Ramirez F, Hollister DW. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991 Jul 25;352(6333):330–334. [PubMed]
  • Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, Puffenberger EG, Hamosh A, Nanthakumar EJ, Curristin SM, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991 Jul 25;352(6333):337–339. [PubMed]
  • Kainulainen K, Sakai LY, Child A, Pope FM, Puhakka L, Ryhänen L, Palotie A, Kaitila I, Peltonen L. Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5917–5921. [PMC free article] [PubMed]
  • McKusick VA. The defect in Marfan syndrome. Nature. 1991 Jul 25;352(6333):279–281. [PubMed]
  • Dobrin PB, Schwarcz TH, Mrkvicka R. Longitudinal retractive force in pressurized dog and human arteries. J Surg Res. 1990 Feb;48(2):116–120. [PubMed]
  • Prockop DJ. Mutations that alter the primary structure of type I collagen. The perils of a system for generating large structures by the principle of nucleated growth. J Biol Chem. 1990 Sep 15;265(26):15349–15352. [PubMed]
  • Kuivaniemi H, Tromp G, Prockop DJ. Mutations in collagen genes: causes of rare and some common diseases in humans. FASEB J. 1991 Apr;5(7):2052–2060. [PubMed]
  • Deak SB, Ricotta JJ, Mariani TJ, Deak ST, Zatina MA, Mackenzie JW, Boyd CD. Abnormalities in the biosynthesis of type III procollagen in cultured skin fibroblasts from two patients with multiple aneurysms. Matrix. 1992 Apr;12(2):92–100. [PubMed]
  • Kontusaari S, Tromp G, Kuivaniemi H, Ladda RL, Prockop DJ. Inheritance of an RNA splicing mutation (G+ 1 IVS20) in the type III procollagen gene (COL3A1) in a family having aortic aneurysms and easy bruisability: phenotypic overlap between familial arterial aneurysms and Ehlers-Danlos syndrome type IV. Am J Hum Genet. 1990 Jul;47(1):112–120. [PMC free article] [PubMed]
  • Kontusaari S, Tromp G, Kuivaniemi H, Romanic AM, Prockop DJ. A mutation in the gene for type III procollagen (COL3A1) in a family with aortic aneurysms. J Clin Invest. 1990 Nov;86(5):1465–1473. [PMC free article] [PubMed]
  • Busuttil RW, Abou-Zamzam AM, Machleder HI. Collagenase activity of the human aorta. A comparison of patients with and without abdominal aortic aneurysms. Arch Surg. 1980 Nov;115(11):1373–1378. [PubMed]
  • Cannon DJ, Read RC. Blood elastolytic activity in patients with aortic aneurysm. Ann Thorac Surg. 1982 Jul;34(1):10–15. [PubMed]
  • Cohen JR, Sarfati I, Ratner L, Tilson D. Alpha 1-antitrypsin phenotypes in patients with abdominal aortic aneurysms. J Surg Res. 1990 Oct;49(4):319–321. [PubMed]
  • Brophy CM, Marks WH, Reilly JM, Tilson MD. Decreased tissue inhibitor of metalloproteinases (TIMP) in abdominal aortic aneurysm tissue: a preliminary report. J Surg Res. 1991 Jun;50(6):653–657. [PubMed]
  • Kuivaniemi H, Tromp G, Prockop DJ. Genetic causes of aortic aneurysms. Unlearning at least part of what the textbooks say. J Clin Invest. 1991 Nov;88(5):1441–1444. [PMC free article] [PubMed]
  • Menashi S, Campa JS, Greenhalgh RM, Powell JT. Collagen in abdominal aortic aneurysm: typing, content, and degradation. J Vasc Surg. 1987 Dec;6(6):578–582. [PubMed]
  • Loidl HR, Brinker JM, May M, Pihlajaniemi T, Morrow S, Rosenbloom J, Myers JC. Molecular cloning and carboxyl-propeptide analysis of human type III procollagen. Nucleic Acids Res. 1984 Dec 21;12(24):9383–9394. [PMC free article] [PubMed]
  • Chu ML, Weil D, de Wet W, Bernard M, Sippola M, Ramirez F. Isolation of cDNA and genomic clones encoding human pro-alpha 1 (III) collagen. Partial characterization of the 3' end region of the gene. J Biol Chem. 1985 Apr 10;260(7):4357–4363. [PubMed]
  • Miskulin M, Dalgleish R, Kluve-Beckerman B, Rennard SI, Tolstoshev P, Brantly M, Crystal RG. Human type III collagen gene expression is coordinately modulated with the type I collagen genes during fibroblast growth. Biochemistry. 1986 Mar 25;25(6):1408–1413. [PubMed]
  • Ala-Kokko L, Kontusaari S, Baldwin CT, Kuivaniemi H, Prockop DJ. Structure of cDNA clones coding for the entire prepro alpha 1 (III) chain of human type III procollagen. Differences in protein structure from type I procollagen and conservation of codon preferences. Biochem J. 1989 Jun 1;260(2):509–516. [PMC free article] [PubMed]
  • Tromp G, Kuivaniemi H, Shikata H, Prockop DJ. A single base mutation that substitutes serine for glycine 790 of the alpha 1 (III) chain of type III procollagen exposes an arginine and causes Ehlers-Danlos syndrome IV. J Biol Chem. 1989 Jan 25;264(3):1349–1352. [PubMed]
  • Tromp G, Kuivaniemi H, Stolle C, Pope FM, Prockop DJ. Single base mutation in the type III procollagen gene that converts the codon for glycine 883 to aspartate in a mild variant of Ehlers-Danlos syndrome IV. J Biol Chem. 1989 Nov 15;264(32):19313–19317. [PubMed]
  • Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Zafarullah K, Kleinert C, Tromp G, Kuivaniemi H, Kontusaari S, Wu YL, Ganguly A, Prockop DJ. G to A polymorphism in exon 31 of the COL3A1 gene. Nucleic Acids Res. 1990 Oct 25;18(20):6180–6180. [PMC free article] [PubMed]
  • Tromp G, Kleinert C, Kuivaniemi H, Prockop DJ. C to T polymorphism in exon 33 of the COL3A1 gene. Nucleic Acids Res. 1991 Feb 11;19(3):681–681. [PMC free article] [PubMed]
  • Gatalica Z, Gibas Z, Martinez-Hernandez A. Dissecting aortic aneurysm as a complication of generalized fibromuscular dysplasia. Hum Pathol. 1992 May;23(5):586–588. [PubMed]
  • Kuivaniemi H, Tromp G, Chu ML, Prockop DJ. Structure of a full-length cDNA clone for the prepro alpha 2(I) chain of human type I procollagen. Comparison with the chicken gene confirms unusual patterns of gene conservation. Biochem J. 1988 Jun 15;252(3):633–640. [PMC free article] [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Gene
    Gene links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • OMIM
    OMIM record citing PubMed
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...