Wyniki wyszukiwania - Biblioteka Nauki

1

COL1A1 mutation analysis in Lithuanian patients with osteogenesis imperfecta

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Benusiene E. , Kucinskas V.

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tom 44

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nr 1

95-102

EN

Osteogenesis imperfecta (OI) is a generalised disorder of connective tissue characterised by an increased fragility of bones and also manifested in other tissues containing collagen type I, by blue sclera, hearing loss, dentinogenesis imperfecta, hyperextensible joints, hernias and easy bruising. OI is dominantly inherited and results in >90% OI cases, caused by mutations in one of the two genes COL1A1 or COL1A2 coding for type I procollagen. The Lithuanian OI database comprises 147 case records covering the period of 1980 ? 2001. Clinical and genealogical analysis of OI cases/families from Lithuania available for examination revealed 18 familial cases of OI type I and 22 sporadic cases: OI type II (3 cases), OI type III (11 cases) and OI type I (8 cases). As a result of their molecular genetic investigation, 11 mutations were identified in the COL1A1 gene in 13 unrelated patients. Of them, nine mutations (E500X, G481A, c.2046insCTCTCTAG, c.1668delT, c.1667insC, c.4337insC, IVS19+1G > A, IVS20-2A > G, IVS22-1G > T) appeared to be novel, i.e. not yet registered in the Human Type I and Type III Collagen Mutations Database (http://www.le.ac.uk/genetics/collagen).

2

Collagens, the basic proteins of the human body

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Czarny-Ratajczak M. , Latos-Bielenska L.-B. A. , Latos-Bielenska A.

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nr 4

317-330

EN

Collagens are structural elements of many tissues in the human body. The family of collagens can be divided into fibrillar and non-fibrillar collagens. The criterion of the classification is the structure of these proteins. Mutations in the genes encoding collagens cause a variety of human diseases that include osteogenesis imperfecta, some forms of osteoporosis, chondrodysplasias, some types of Ehlers-Danlos syndrome, arterial and intracranial aneurysms, epidermolysis bullosa and the renal disease known as Alport syndrome. The detection of mutations is important both scientifically and clinically. Defining the molecular defects underlying a disorder helps in the understanding of not only the properties of the mutated protein but also the function of the normal protein. Even though many mutations in the genes encoding collagens have been described, the pathogenic consequences of some of the mutations are not fully understood. The important rationale for mutation detection is the clinical use of molecular diagnostics in genetic counselling and differential diagnosis.

3

Molecular findings in Brazilian patients with osteogenesis imperfecta

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Reis F. C. , Alexandrino F. , Steiner C. E. , Norato D. Y. J. , Cavalcanti D. P. , Sartorato E. L.

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2005

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tom 46

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nr 1

105-108

EN

Osteogenesis imperfecta (OI) is a genetic disorder of increased bone fragility and low bone mass. Severity varies widely, ranging from intrauterine fractures and perinatal lethality to very mild forms without fractures. Most patients with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2 genes that encode the chains of type I procollagen, the major protein in bones. Hence, the aim of the present study was to identify mutations in the COL1A1 gene in 13 unrelated Brazilian OI patients. This is the first molecular study of OI in Brazil. We found 6 mutations, 4 of them novel (c.1885delG, p.P239A, p.G592S, p.G649D) and 2 previously described (p.R237X and p.G382S). Thus, the findings show that there are no prevalent mutations in our sample, and that their distribution is similar to that reported by other authors, with preponderance of substitutions for glycine in the triple helix domain, causing OI types II, III and IV.

4

Molecular studies in osteogenesis imperfecta (OI). I. Clinical analysis of patients with osteogenesis imperfecta

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Pietrzyk J. J. , Kruczek A. , Sucharski P. , Piatkowska E.

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tom 39

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nr 4

331-348

EN

The goal of this study is to develop optimal diagnostic methods for osteogenesis imperfecta (OI), which will allow to distinguish familial from spontaneous cases and can be used in prenatal diagnostics as well. The paper summarizes the clinical part of the study, in which 69 families were analyzed. The families with OI were registered, their pedigrees were studied, a clinical classification of the disease was carried out and the dermatoglyphics of the affected patients were analyzed. Based on the above results a diagnostic algorithm was elaborated.

5

In vitro culture of human epithelial cells on a modified xenogenic collagen support

100%

Lesiak-Cyganowska E. , Sladowski D. , Jankowska E. , Komender J.

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nr 3

253-259

EN

Human epithelial cells (HeLa, HaCaT, NHK) were cultured in vitro on chemically modified collagen membranes. Adhesion to the support was measured by estimation of the percentage of adhering 51Cr-labeled cells. Proliferation was estimated with the XTT test. Morphological observations of cells growing on HCl-treated collagen were performed using histological and electron microscopic techniques. HCl and trypsin-modified xenogenic collagen was found to be a good support for human cells in vitro. EDTA-incubated collagen enhanced neither adhesion nor proliferation. The best adhesion and proliferation were found on HCl-treated collagen, depending, however, on the kind of cells.

6

Oxidative modification of type II collagen differentially affects its arthritogenic and tolerogenic capacity in experimental arthritis

88%

Marcinkiewicz J. , Biedron R. , Maresz K. , Kwasny-Krochin B. , Bobek M. , Kontny E. , Maslinski W. , Chain B.

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nr 4

284-291

EN

Oxidative modification of proteins affects their biological properties. Previously we have shown that hypochlorite (HOCl), the product of activated neutrophils, enhances protein immunogenecity. Collagen type II, a primary component of cartilage, is commonly used in the induction of arthritis in animals (CIA). The aim of this study was to examine whether HOCl may affect immunogenic, tolerogenic, and arthritogenic properties of collagen. DBA/J mice were injected with either native (CNAT) or chlorinated collagen (CHOCl) to induce arthritis. The effect of chlorination on collagen properties was measured by evaluation of incidence and severity of CIA. Moreover, the concentration of serum anti-collagen IgG antibodies and myeloperoxidase (MPO) activity in inflamed joints was determined. Mice immunized with CNAT in adjuvant developed arthritis (CIA) with an incidence of 69%. CNAT also exerted tolerogenic properties when injected intravenously either before or shortly after primary immunization, resulting in decreased incidence and severity of CIA, reduced MPO activity in inflamed joints, and lowered serum levels of anti-CNAT IgG antibodies. Chlorination of collagen significantly diminished its ability to induce CIA and to trigger generation of anti-CNAT IgG antibodies. Interestingly, chlorination did not affect tolerogenic properties of collagen administered prior to primary immunization with CNAT. These results suggest that chlorination of collagen may selectively affect functional epitopes of collagen. It is likely that in inflamed joints, neutrophil-derived HOCl, in some circumstances, will destroy arthritogenic and immunogenic B cell epitopes, while regulatory T cell epitopes will be preserved.

7

Two novel COL1A1 mutations in patients with osteogenesis imperfecta (OI) affect the stability of the collagen type I triple-helix

88%

Witecka J. , Augusciak-Duma A. M. , Kruczek A. , Szydlo A. , Lesiak M. , Krzak M. , Pietrzyk J. J. , Mannikko M. , Sieron A. L.

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nr 3

283-295

EN

Osteogenesis imperfecta (OI) is a bone dysplasia caused by mutations in the COL1A1 and COL1A2 genes. Although the condition has been intensely studied for over 25 years and recently over 800 novel mutations have been published, the relation between the location of mutations and clinical manifestation is poorly understood. Here we report missense mutations in COL1A1 of several OI patients. Two novel mutations were found in the D1 period. One caused a substitution of glycine 200 by valine at the N-terminus of D1 in OI type I/IV, lowering collagen stability by 50% at 34?C. The other one was a substitution of valine 349 by phenylalanine at the C-terminus of D1 in OI type I, lowering collagen stability at 37.5?C. Two other mutations, reported before, changed amino residues in D4. One was a lethal substitution changing glycine 866 to serine in genetically identical twins with OI type II. That mutated amino acid was near the border of D3 and D4. The second mutation changed glycine 1040 to serine located at the border of D4 and D0.4, in a proband manifesting OI type III, and lowered collagen stability at 39?C (2?C lower than normal). Our results confirm the hypothesis on a critical role of the D1 and D4 regions in stabilization of the collagen triple-helix. The defect in D1 seemed to produce a milder clinical type of OI, whereas the defect in the C-terminal end of collagen type caused the more severe or lethal types of OI.