Summary
The structure and metabolism of type I and III collagens were studied in fibroblast cultures and dermis from 25 unrelated patients including 23 with typical Marfan syndrome and two infants with a very severe clinical form of this syndrome. Electrophoretic analysis of collagen α-chains, as well as one- and two-dimensional electrophoresis of collagen cyanogen bromide peptides, failed to show any evidence of primary structure defects or overmodification of lysine residues in these collagens. The proportion of hydroxylated prolyl residues in isolated α1(I) chains was also normal. There was a minimal increase in the proportion of type III collagen produced by nine cultures. The findings in this study indicate that the underlying molecular defects in the patients studied are unlikely to involve the structure of the main fibrillar type I and III collagens.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bateman, J. F., Mascara, T., Chan, D. and Cole, W. G. Abnormal type I collagen metabolism by cultured fibroblasts in lethal perinatal osteogenesis imperfecta.Biochem. J. 217 (1984) 103–115
Bateman, J. F., Chan, D., Mascara, T., Rogers, J. G. and Cole, W. G. Collagen defects in lethal perinatal osteogenesis imperfecta.Biochem. J. 240 (1986) 699–708
Bateman, J. F., Chan, D., Walker, I., Rogers, J. G. and Cole, W. G. Lethal osteogenesis imperfecta due to a substitution of arginine for glycine at residue 391 of the α1(I) chain of type I collagen.J. Biol. Chem. 262 (1987) 7021–7027
Byers, P. H., Siegel, R. C., Peterson, K. E., Rowe, D. W., Holbrook, K. A., Smith, L. T., Chang, Y. and Fu, J. C. C. Marfan syndrome: abnormal α2 chain in type I collagen.Proc. Natl. Acad. Sci. USA 78 (1981) 7745–7749
Chemke, J., Nisani, R., Fiegl, A., Garty, R., Cooper, M., Barash, Y. and Duskin, D. Homozygosity for autosomal dominant Marfan syndrome.J. Med. Genet. 21 (1984) 173–177
Cole, W. G. and Chan, D. Analysis of the heterogeneity of human collagens by two-dimensional polyacrylamide-gel electrophoresis.Biochem. J. 197 (1981) 377–383
Cole, W. G., Chan, D., Chambers, G. W., Walker, I. D. and Bateman, J. F. Deletion of 24 amino acids from the proα1(I) chain of type I procollagen in a patient with the Ehlers-Danlos syndrome type VII.J. Biol. Chem. 261 (1986) 5496–5503
Dalgleish, R., Williams, G. and Hawkins, J. R. Length polymorphism in the pro α2(I) collagen gene: an alternative explanation in a case of Marfan syndrome.Hum. Genet. 73 (1986) 91–92
Dalgleish, R., Hawkins, J. R. and Keston, M. Exclusion of the α2(I) and α1(III) collagen genes as the mutant loci in a Marfan syndrome family.J. Med. Genet. 24 (1987) 148–151
Francomano, C. A., Streeten, E. A., Meyers, D. A. and Pyeritz, R. E., Marfan syndrome: exclusion of genetic linkage to three major collagen genes.Am. J. Med. Genet. 29 (1988) 457–462
Halbritter, R., Aumailley, M., Rackwitz, R., Kreig, T. and Muller, P.K. Case report and study of collagen metabolism in Marfan's syndrome.Klin. Wochenschr. 59 (1981) 83–90
Henke, E., Leader, M., Tajima, S., Pinnell, S., Kaufman, R. A 38 base pair insertion in the pro α2(I) collagen gene of a patient with Marfan syndrome.J. Cell Biochem. 27 (1985) 169–174
Hollister, D. W., Sakai, L. K. and Pyeritz, R. E. Marfan syndrome: abnormality of the microfibrillar array.Clin. Res. 35 (1987) 211A
Muller, K. P., Nerlich, A. G., Kunze, D. and Muller, P. K. Studies on collagen metabolism in the Marfan syndrome.Eur. J. Clin. Invest. 17 (1987) 218–225
Ogilvie, D. J., Wordsworth, B. P., Priestley, L. M. Dalgleish, R., Schmidtke, J., Zoll, B. and Sykes, B. C. Segregation of all four major fibrillar collagen genes in the Marfan syndrome.Am. J. Hum. Genet. 41 (1987) 1071–1082
Phillips, C. L., Shrago, A. W., Pinnell, S. R. and Wenstrup, R. J. DNA sequence analysis of alpha 2(I) collagen from an individual with the Marfan phenotype.Ann. NY Acad. Sci. (1989) (in press)
Pope, F. M., Nicholls, A. C., Lewkonia, R. M., Halme, T., Dorrance, D. E. and Pomerance, A. Clinical and genetic heterogeneity of the Marfan syndrome.Curr. Probl. Dermatol. 17 (1987) 95–110
Pyeritz, R. E. and McKusick, V. A. The Marfan syndrome: diagnosis and management.N. Engl. J. Med. 300 (1979) 772–777
Tseng, S. C. G., Stern, R. and Nitecki, D. E. A new rapid method for quantitating radioactive proline, 4-hydroxyproline and 3-hydroxyproline.Anal. Biochem. 102 (1980) 291–299
Tsipouras, P. and Ramirez, F. Genetic disorders of collagen.J. Med. Genet. 24 (1987) 2–8
Tsipouras, P., Borresen, A-L., Bamforth, S., Harper, P. S. and Berg, K. Marfan syndrome: exclusion of genetic linkage to the COL1A2 gene.Clin. Genet. 30 (1986) 428–432
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Harley, V.R., Chan, D., Rogers, J.G. et al. Marfan syndrome: Absence of type I or III collagen structural defects in 25 patients. J Inherit Metab Dis 13, 219–226 (1990). https://doi.org/10.1007/BF01799689
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01799689