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. 1992 Jun;29(6):375–380. doi: 10.1136/jmg.29.6.375

Detection and characterisation of an overmodified type III collagen by analysis of non-cutaneous connective tissues in a patient with Ehlers-Danlos syndrome IV.

L Nuytinck 1, P Narcisi 1, A Nicholls 1, J P Renard 1, F M Pope 1, A De Paepe 1
PMCID: PMC1015985  PMID: 1619632

Abstract

The clinical and biochemical observations in a patient with a mild form of Ehlers-Danlos syndrome (EDS) type IV are described. The patient's skin fibroblasts produced markedly diminished amounts of type III collagen. SDS-polyacrylamide gel electrophoresis of collagens produced by cells obtained from other, non-cutaneous tissues showed two forms of collagen alpha 1(III) chains, a normal and a slow migrating, mutant form. Further analysis confirmed that the type III collagen molecules containing mutant alpha chains which were overmodified had a lower thermal stability and were poorly secreted into the extracellular medium. The protein defect was mapped by in situ cyanogen bromide digestion and was located in alpha 1(III) CB9, the C-terminal peptide of the collagen triple helix. This study shows that non-cutaneous connective tissues can be a useful source for the study of type III collagen defects in patients with EDS type IV.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bonadio J., Byers P. H. Subtle structural alterations in the chains of type I procollagen produce osteogenesis imperfecta type II. Nature. 1985 Jul 25;316(6026):363–366. doi: 10.1038/316363a0. [DOI] [PubMed] [Google Scholar]
  2. Bruckner P., Prockop D. J. Proteolytic enzymes as probes for the triple-helical conformation of procollagen. Anal Biochem. 1981 Jan 15;110(2):360–368. doi: 10.1016/0003-2697(81)90204-9. [DOI] [PubMed] [Google Scholar]
  3. Byers P. H. Brittle bones--fragile molecules: disorders of collagen gene structure and expression. Trends Genet. 1990 Sep;6(9):293–300. doi: 10.1016/0168-9525(90)90235-x. [DOI] [PubMed] [Google Scholar]
  4. Byers P. H., Holbrook K. A., Barsh G. S., Smith L. T., Bornstein P. Altered secretion of type III procollagen in a form of type IV Ehlers-Danlos syndrome. Biochemical studies in cultured fibroblasts. Lab Invest. 1981 Apr;44(4):336–341. [PubMed] [Google Scholar]
  5. Byers P. H., Holbrook K. A., McGillivray B., MacLeod P. M., Lowry R. B. Clinical and ultrastructural heterogeneity of type IV Ehlers-Danlos syndrome. Hum Genet. 1979 Mar 12;47(2):141–150. doi: 10.1007/BF00273196. [DOI] [PubMed] [Google Scholar]
  6. Cikrit D. F., Miles J. H., Silver D. Spontaneous arterial perforation: the Ehlers-Danlos specter. J Vasc Surg. 1987 Feb;5(2):248–255. [PubMed] [Google Scholar]
  7. Cole W. G., Chiodo A. A., Lamande S. R., Janeczko R., Ramirez F., Dahl H. H., Chan D., Bateman J. F. A base substitution at a splice site in the COL3A1 gene causes exon skipping and generates abnormal type III procollagen in a patient with Ehlers-Danlos syndrome type IV. J Biol Chem. 1990 Oct 5;265(28):17070–17077. [PubMed] [Google Scholar]
  8. Kontusaari S., Tromp G., Kuivaniemi H., Romanic A. M., Prockop D. J. 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. doi: 10.1172/JCI114863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  10. Laskey R. A., Mills A. D. Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. Eur J Biochem. 1975 Aug 15;56(2):335–341. doi: 10.1111/j.1432-1033.1975.tb02238.x. [DOI] [PubMed] [Google Scholar]
  11. Lee B., D'Alessio M., Vissing H., Ramirez F., Steinmann B., Superti-Furga A. Characterization of a large deletion associated with a polymorphic block of repeated dinucleotides in the type III procollagen gene (COL3A1) of a patient with Ehlers-Danlos syndrome type IV. Am J Hum Genet. 1991 Mar;48(3):511–517. [PMC free article] [PubMed] [Google Scholar]
  12. Nicholls A. C., De Paepe A., Narcisi P., Dalgleish R., De Keyser F., Matton M., Pope F. M. Linkage of a polymorphic marker for the type III collagen gene (COL3A1) to atypical autosomal dominant Ehlers-Danlos syndrome type IV in a large Belgian pedigree. Hum Genet. 1988 Mar;78(3):276–281. doi: 10.1007/BF00291676. [DOI] [PubMed] [Google Scholar]
  13. Pope F. M., Martin G. R., Lichtenstein J. R., Penttinen R., Gerson B., Rowe D. W., McKusick V. A. Patients with Ehlers-Danlos syndrome type IV lack type III collagen. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1314–1316. doi: 10.1073/pnas.72.4.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pope F. M., Narcisi P., Nicholls A. C., Liberman M., Oorthuys J. W. Clinical presentations of Ehlers Danlos syndrome type IV. Arch Dis Child. 1988 Sep;63(9):1016–1025. doi: 10.1136/adc.63.9.1016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pope F. M., Nicholls A. C., Narcisi P., Temple A., Chia Y., Fryer P., De Paepe A., De Groote W. P., McEwan J. R., Compston D. A. Type III collagen mutations in Ehlers Danlos syndrome type IV and other related disorders. Clin Exp Dermatol. 1988 Sep;13(5):285–302. doi: 10.1111/j.1365-2230.1988.tb00709.x. [DOI] [PubMed] [Google Scholar]
  16. Prockop D. J., Kivirikko K. I. Heritable diseases of collagen. N Engl J Med. 1984 Aug 9;311(6):376–386. doi: 10.1056/NEJM198408093110606. [DOI] [PubMed] [Google Scholar]
  17. Richards A. J., Lloyd J. C., Ward P. N., De Paepe A., Narcisi P., Pope F. M. Characterisation of a glycine to valine substitution at amino acid position 910 of the triple helical region of type III collagen in a patient with Ehlers-Danlos syndrome type IV. J Med Genet. 1991 Jul;28(7):458–463. doi: 10.1136/jmg.28.7.458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Stolle C. A., Pyeritz R. E., Myers J. C., Prockop D. J. Synthesis of an altered type III procollagen in a patient with type IV Ehlers-Danlos syndrome. A structural change in the alpha 1(III) chain which makes the protein more susceptible to proteinases. J Biol Chem. 1985 Feb 10;260(3):1937–1944. [PubMed] [Google Scholar]
  19. Superti-Furga A., Gugler E., Gitzelmann R., Steinmann B. Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen. J Biol Chem. 1988 May 5;263(13):6226–6232. [PubMed] [Google Scholar]
  20. Superti-Furga A., Steinmann B. Impaired secretion of type III procollagen in Ehlers-Danlos syndrome type IV fibroblasts: correction of the defect by incubation at reduced temperature and demonstration of subtle alterations in the triple-helical region of the molecule. Biochem Biophys Res Commun. 1988 Jan 15;150(1):140–147. doi: 10.1016/0006-291x(88)90497-4. [DOI] [PubMed] [Google Scholar]
  21. Sykes B., Puddle B., Francis M., Smith R. The estimation of two collagens from human dermis by interrupted gel electrophoresis. Biochem Biophys Res Commun. 1976 Oct 18;72(4):1472–1480. doi: 10.1016/s0006-291x(76)80180-5. [DOI] [PubMed] [Google Scholar]
  22. Temple A. S., Hinton P., Narcisi P., Pope F. M. Detection of type III collagen in skin fibroblasts from patients with Ehlers-Danlos syndrome type IV by immunofluorescence. Br J Dermatol. 1988 Jan;118(1):17–26. doi: 10.1111/j.1365-2133.1988.tb01745.x. [DOI] [PubMed] [Google Scholar]
  23. Tromp G., Kuivaniemi H., Shikata H., Prockop D. J. 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] [Google Scholar]
  24. Tromp G., Kuivaniemi H., Stolle C., Pope F. M., Prockop D. J. 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] [Google Scholar]
  25. Tsipouras P., Byers P. H., Schwartz R. C., Chu M. L., Weil D., Pepe G., Cassidy S. B., Ramirez F. Ehlers-Danlos syndrome type IV: cosegregation of the phenotype to a COL3A1 allele of type III procollagen. Hum Genet. 1986 Sep;74(1):41–46. doi: 10.1007/BF00278783. [DOI] [PubMed] [Google Scholar]

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