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1. |
Papers presented at the Fourth International Conference on Osteogenesis Imperfecta: Introduction |
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American Journal of Medical Genetics,
Volume 45,
Issue 2,
1993,
Page 139-139
Peter Byers,
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ISSN:0148-7299
DOI:10.1002/ajmg.1320450202
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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2. |
Regulation of expression of the type I collagen genes |
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American Journal of Medical Genetics,
Volume 45,
Issue 2,
1993,
Page 140-151
James L. Slack,
Deann J. Liska,
Paul Bornstein,
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摘要:
AbstractThe identification and functional analysis of DNA‐protein interactions in the intronic and 5′ flanking regions of the type I collagen genes has begun to define a series of cis‐elements and trans‐acting factors which regulate transcription of these genes. Studies such as these will eventually be expected to elucidate the mechanisms responsible for coordinate transcription of the α1 and α2 genes, a question which remains central to the field of collagen research. Although it is relatively straightforward to define sites of DNA‐protein binding, interpretation of the functional importance of such interactions can be extremely complex. Furthermore, while mutation or deletion of a particular binding site may alter the functional activity of a construct transfected into cultured cells, there is no guarantee that a similar change will have the same effect in vivo, where the entire gene locus is present in its native chromosomal context. Nevertheless, these kinds of in vitro studies offer the best current approach to defining and isolating transcription factors that control expression of the α1 and α2 genes. Ultimately, it will be necessary to test the activity of such factors (and their respective cis‐elements) in defined
ISSN:0148-7299
DOI:10.1002/ajmg.1320450203
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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3. |
Thermal stability and folding of the collagen triple helix and the effects of mutations in osteogenesis imperfecta on the triple helix of type I collagen |
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American Journal of Medical Genetics,
Volume 45,
Issue 2,
1993,
Page 152-162
Hans Peter Bächinger,
Nicholas P. Morris,
Janice M. Davis,
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摘要:
AbstractOsteogenesis imperfecta (OI) is an inherited disease in which 90% of the cases result from mutations in the 2 genes, proα1 and proα2, coding for type I collagen. Type I collagen is a trimeric molecule, (α1)2α2, which is dominated both structurally and functionally by the 300 nm triple‐helical domain. Most OI mutations occur in this domain and almost all point mutations result in the substitution of other amino acids for the obligate glycine which occurs at every third residue. The phenotypic effects of these mutations are frequently attributed in part to alterations in the stability and rate of folding of the triple helix. In order to better understand the relationship between glycine substituions and stability we review current concepts of the forces governing triple helical stability, denaturational and predenaturational unfolding, and the techniques of measuring stability. From observations on the stability of several collagen types as well as synthetic tripeptides, we present a model for stability based on the contribution of individual and neighboring tripeptide units to the local stability. Although in preliminary form, this empirical model can account for the observed shifts in the Tmof many of the point mutations described. The folding of the triple helix is reviewed. The involvement of peptidyl prolyl cis‐trans isomerase in this process in vivo is demonstrated by the inhibition of collagen folding in fibroblasts by cyclosporin A. An hypothesis based on the relationship between the thermal stability at the site of mutation and the propensity for renucleation of folding is p
ISSN:0148-7299
DOI:10.1002/ajmg.1320450204
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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4. |
Formation of mineralized nodules by bone derived cells in vitro: A model of bone formation? |
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American Journal of Medical Genetics,
Volume 45,
Issue 2,
1993,
Page 163-178
Jon N. Beresford,
Steven E. Graves,
Caroline A. Smoothy,
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摘要:
AbstractThe identification of the factors which regulate the proliferation and differentiation of cells of the osteoblast lineage remains one of the major challenges in the field of bone cell biology. Although considerable progress has been made in the isolation and culture of cells of the osteoblast lineage from both animal and, more recently, human bone, uncertainties have persisted as to the extent to which these cell populations retain the ability to differentiate into functional osteoblasts in vitro.The formation in vitro of mineralized nodules that exhibit the morphological, ultrastructural and biochemical characteristics of embryonic/woven bone formed in vivo, represents the first evidence that the differentiation of functional osteoblasts can occur in cultures of isolated animal bone‐derived cell populations. It is clear, however, that the culture conditions employed at present only permit a small number of cells to differentiate to the extent of being capable of organising their extracellular matrix into a structure that resembles that of bone. Moreover, it has generally been found that the reproducible mineralization of this extracellular matrix requires supplementation of the culture medium with mM concentrations of β‐GP, which raises doubts as to the physiological relevance of this process.The formation of nodules has also been observed in cultures of human bone‐derived cells. As found in cultures of animal bonederived cells, reproducible mineralization of these nodules will occur in the presence of β‐GP. We have shown, however, that in the presence of the long acting ascorbate analogue Asc‐2‐P, the formation and mineralization of nodules can occur in the absence of β‐GP. The nodules formed in human bone‐derived cell cultures have yet to be characterized as rigorously as those formed in cultures of animal bone‐derived cells and thus it remains to be shown that they resemble
ISSN:0148-7299
DOI:10.1002/ajmg.1320450205
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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5. |
In vitro chondrogenesis in human chondrodysplasias |
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American Journal of Medical Genetics,
Volume 45,
Issue 2,
1993,
Page 179-182
William A. Horton,
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摘要:
AbstractBone morphogenesis depends on the sequential expression of multiple genes that first allow formation of mesenchymal anlagen, their replacement by cartilage models, and finally, the synthesis of new bone at growth plates. These processes require orchestration of synthesis of multiple collagens, proteoglycans and glycoproteins, the genes for many of which have been isolated and are being studied. Several genes carry mutations which are responsible for the chondrodysplasia phenotypes and can be studied at the gene level or by examining their expression in cultured chondrocytes.
ISSN:0148-7299
DOI:10.1002/ajmg.1320450206
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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6. |
Natural history of blue sclerae in osteogenesis imperfecta |
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American Journal of Medical Genetics,
Volume 45,
Issue 2,
1993,
Page 183-186
D. Sillence,
B. Butler,
M. Latham,
K. Barlow,
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摘要:
AbstractScleral hue is an important sign which distinguishes 2 broad groupings of patients, those with and those without blue sclerae with non‐lethal osteogenesis imperfecta (OI). Individuals with OI type I have distinctly blue sclerae which remain intensely blue throughout life. In OI type III and OI type IV the sclerae may also be blue at birth and during infancy, but the intensity fades with time such that these individuals have sclerae of normal hue by adolescence and adult lif
ISSN:0148-7299
DOI:10.1002/ajmg.1320450207
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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7. |
Osteogenesis imperfecta: The distinction from child abuse and the recognition of a variant form |
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American Journal of Medical Genetics,
Volume 45,
Issue 2,
1993,
Page 187-192
Colin R. Paterson,
James Burns,
Susan J. McAllion,
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摘要:
AbstractUnexplained fractures are characteristic of both osteogenesis imperfecta (OI) and nonaccidental injury (NAI) but in most cases the diagnosis is straightforward. However, in a few OI patients an initial diagnosis of NAI is made. Factors contributing to such difficulties include failure to recognise that OI can occur without a family history, without blue sclerae, without osteopenia, an excess of Wormian bones, or with metaphyseal fractures.In addition we report on 39 patients with an unusual history in that fractures only occurred in the first year of life. Rib fractures, metaphyseal abnormalities and periosteal reactions were common. The initial diagnosis was usually OI if the fractures occurred in hospital, but NAI if they appeared to have been sustained at home. Additional findings such as anaemia, vomiting, hepatomegaly, and apnoeic attacks were often found in these patients. The disorder has some similarities to the syndrome of infantile copper deficiency. Like the latter it is particularly common in preterm infants and in twins. Therefore, we are attempting to examine the incidence of significant hypocupraemia in unselected preterm infants.We suggest that the likely cause of this “temporary brittle bone disease” is a temporary deficiency of an enzyme, perhaps a metalloenzyme, involved in the post‐translational processing of col
ISSN:0148-7299
DOI:10.1002/ajmg.1320450208
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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8. |
Heritable dentin defects: Nosology, pathology, and treatment |
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American Journal of Medical Genetics,
Volume 45,
Issue 2,
1993,
Page 193-200
Helena Ranta,
Pirjo‐Liisa Lukinmaa,
Janna Waltimo,
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摘要:
AbstractHeritable dentin defects have been divided into 2 main categories: dentinogenesis imperfecta (DI) and dentin dysplasia (DD). Recent studies have shown that they share many features in common. Of the connective tissue diseases, only osteogenesis imperfecta (OI) has been linked to these disorders. So far, no definitive relation between the type of OI and the dental involvement can be established. Familial occurrence of DI with OI cannot be comprehensively explained by mutations in type I collagen genes. No information about the gene defects in DD is available. At the ultrastructural level, the organization of the normally cross‐striated collagen fibers in the dentin matrix varies markedly in patients affected by D
ISSN:0148-7299
DOI:10.1002/ajmg.1320450209
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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9. |
Non‐invasive prenatal diagnosis of osteogenesis imperfecta |
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American Journal of Medical Genetics,
Volume 45,
Issue 2,
1993,
Page 201-206
Elizabeth M. Thompson,
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摘要:
AbstractThe main mode of non‐invasive prenatal diagnosis of osteogenesis imperfecta (OI) is fetal imaging, either by radiography or detailed ultrasonography. Radiography is more of historical interest and ultrasonography is in practice virtually exclusively used for non‐invasive second trimester diagnosis of OI. Both methods have also been reported later in pregnancy when diagnosis allows the most appropriate method of delivery to be planned. For example, a caesarean section can be avoided if the fetus is shown to have a form of OI associated with limited survival.Ultrasonography is useful mainly for prenatal diagnosis of the severe forms of OI, especially the perinatally lethal forms (Sillence type II) and to a lesser extent for the severe progressively deforming forms (Sillence types III and III/IV). For the milder varieties of OI (Sillence types I and IV), many cases will be missed by scans. Invasive methods of prenatal diagnosis of OI (principally chorion villous sampling) are used for families with the milder dominant forms of OI and in severe forms of OI in which the actual biochemical or molecular defect in type I collagen is known.Many cases of type II OI and a few of type III have now been reported which were detected by scans before 20 weeks gestation, the earliest being at 15 weeks, for type IIA OI. These include cases not only at genetic risk but also sporadic cases in which scans were done either routinely or for obstetric indications.The ultrasonic abnormalities which are found include reduced echogenicity, multiple fractures, and deformity of the long bones, ribs and skull. There is a marked reduction of long bone length on measurement. The abnormalities are more severe in type II OI than in type III.No false negative diagnoses have yet been reported for severe OI. Ultrasonography is a reliable mode of prenatal diagnosis for a pregnancy at risk of type II OI and probably also for type III, although more reports for the latter are needed to give more information about the likelihood of false negative diagnoses in this form of OI. For pregnancies at risk of types II and III OI, serial scans from 14 weeks gestation can be offered. An experienced operator, using a good realitime scanner should be able to detect type II OI by at least 17 weeks gestation, and type III OI by 19 to 20 weeks. In future, it may be possible to diagnose type II OI in the first trimester by ultrasound using an intravaginal transdu
ISSN:0148-7299
DOI:10.1002/ajmg.1320450210
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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10. |
Psychosocial aspects of osteogenesis imperfecta: An update |
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American Journal of Medical Genetics,
Volume 45,
Issue 2,
1993,
Page 207-211
David E. C. Cole,
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摘要:
AbstractOsteogenesis imperfecta (OI) is an inherited disorder in which affected individuals are stigmatized by virtue of physical differences from their peers. The extent to which these differences alter life style depend on the severity of the disorder, its natural history, the extent to which it affects social integration, the effect on physical appearance, and the presence of other affected family members. Some of these factors may adversely influence the ability of affected individuals to effectively adjust to their social and work environment and recognition of these factors may aid individuals and helpers in easing the path to a constructive life.
ISSN:0148-7299
DOI:10.1002/ajmg.1320450211
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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