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Mutations near amino end of alpha1(I) collagen cause combined osteogenesis imperfecta/Ehlers-Danlos syndrome by interference with N-propeptide processing


, : Mutations near amino end of alpha1(I) collagen cause combined osteogenesis imperfecta/Ehlers-Danlos syndrome by interference with N-propeptide processing. Journal of Biological Chemistry 280(19): 19259-19269

Patients with OI/EDS form a distinct subset of osteogenesis imperfecta (OI) patients. In addition to skeletal fragility, they have characteristics of Ehlers-Danlos syndrome (EDS). We identified 7 children with types III or IV OI, plus severe large and small joint laxity and early progressive scoliosis. In each child with OI/EDS, we identified a mutation in the first 90 residues of the helical region of alpha1(I) collagen. These mutations prevent or delay removal of the procollagen N-propeptide by purified N-proteinase (ADAMTS-2) in vitro and in pericellular assays. The mutant pN-collagen which results is efficiently incorporated into matrix by cultured fibroblasts and osteoblasts and is prominently present in newly incorporated and immaturely cross-linked collagen. Dermal collagen fibrils have significantly reduced cross-sectional diameters, corroborating incorporation of pN-collagen into fibrils in vivo. Differential scanning calorimetry revealed that these mutant collagens are less stable than the corresponding procollagens, which is not seen with other type I collagen helical mutations. These mutations disrupt a distinct folding region of high thermal stability in the first 90 residues at the amino end of type I collagen and alter the secondary structure of the adjacent N-proteinase cleavage site. Thus, these OI/EDS collagen mutations are directly responsible for the bone fragility of OI and indirectly responsible for EDS symptoms, by interference with N-propeptide removal.

US$19.90

PMID: 15728585

DOI: 10.1074/jbc.M414698200


Other references

Jones, D.N.; Lew, W.; Wycherley, A.G., 1994: Hepatic uptake of a bone scan agent (99mTc-MDP) in a patient with amyloidosis associated with plasma cell dyscrasia. This case report describes diffuse hepatic uptake of a diphosphonate bone scan agent (Technetium-99m-MDP) in a patient with amyloidosis associated with a plasma cell dyscrasia. Amyloid infiltration is one of the more rare, but well recognized, cau...

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Pavlovsky E.V., 1960: Problema vozrasta kristallicheskikh slantsev Tsentralnogo massiva Frantsii. On the basis of a review of the literature, concludes that rocks composing the so-called core of the Central Massif of France are Precambrian. Characteristic of the entire core region is the folding at the end of the Precambrian, progressive topoc...

Bottacini, A.; Scalia, P.; Goss, C., 2017: Shared decision making in Italy: An updated revision of the current situation. The aim of this paper is to update the previous review on the state of patient and public participation in healthcare in Italy. Policymakers consider patient involvement an important aspect in health care decisions and encourage patients to active...

Anderson D.T., 1974: International series of monographs in pure and applied biology division zoology vol 50 embryology and phylogeny in annelids and arthropods. International Series In Pure And Applied Biology Zoology Division:

Berschneider, B.; Wieland, M.; Rubini, M.; Hartig, Jörg.S., 2009: Small-molecule-dependent regulation of transfer RNA in bacteria. Angewandte Chemie 48(41): 7564-7567

Paramasivam, S.; Niimi, Y.; Fifi, J.; Berenstein, A., 2014: Onyx embolization using dual-lumen balloon catheter: initial experience and technical note. Onyx as an embolization agent for the management of vascular malformation is well established. We report our initial experience with dimethyl-sulphoxide (DMSO) compatible double lumen balloon catheters used for Onyx embolization. Between December...

Javornik, B., 1984: Identification of wheat varieties by means of gliadin electrophoresis. Zbornik Biotehniske fakultete univerze Edvarda Kardelja v Ljubljani: Kmetijstvoub 1984) 41(41): 17-28

Kroemer, G.; Brezinschek, H.P.; Faessler, R.; Schauenstein, K.; Wick, G., 1988: Physiology and pathology of an immunoendocrine feedback loop. Research in autoimmunity has tended to focus on lymphocytes and their products at the expense of other factors that also contribute to the development of disease. Here, Guido Kroemer and colleagues stress that aberrations in immunoendocrinological...

Ontermaa, E.; Haines, J.R.inholde, V., 1996: User perspective on laboratory analysis and its reliability. Proceedings of the annual meeting of the Florida State Horticultural Society09(109): 81-85