PATHOLOGY OF INBORN SKELETAL DISEASES

胶原蛋白结构中的先天分子缺陷正在被表征 在各种骨骼疾病中。重点放在成骨方面 不完美，埃勒斯-丹洛斯综合征和某些软骨营养不良。的 特别令人感兴趣的是导致结构突变的疾病 细胞外基质中表达的胶原蛋白及其对血管生成的影响 胶原蛋白的聚合和交联。微电子技术的应用 蛋白质化学技术是组织活检的主题 工作。 成骨不完美的目标是更好地理解 I型胶原中突变的多样性都会导致骨骼脆化。 通过研究已知患者的骨组织(手术和尸检) 分子缺陷，突变表达的程度和 持续存在于细胞外的交联骨基质将被检查。是 这种疾病主要是由于胶原蛋白生成不足，而不是 结构不充分的胶原分子形成的后果 矩阵？同样，结构性突变和 Ehler-Danlos综合征患者胶原蛋白翻译后缺陷 Vii将得到更详细的定义。 将努力揭示遗传的结构性缺陷 软骨特异性胶原(II型和IX型)是窗帘的起因 各种形式的软骨营养不良，包括广义的 脊柱骨骺发育不良和遗传性发育不良。这个 人类II型胶原基因存在多态的可能性 可能解释了观察到的自然变化 在人体软骨胶原蛋白的交联度方面，将进行测试。 影响交联型AS的II型胶原的遗传突变 家族性骨关节病的病因也将被检查。 目的是了解胶原蛋白某些特性的重要性。 结构，例如控制交联反应的结构，在 决定功能。通过了解稀有的影响 先天突变，所以胶原蛋白和它们的正常性质 人们可以更好地欣赏各种变化。

Inborn molecular defects in collagen structure are being characterized in various skeletal diseases. The emphasis is on osteogenesis imperfecta, Ehlers Danlos syndrome and certain chondrodystrophies. Of particular interest are diseases that result in structural mutations of collagen expressed in the extracellular matrix and their effects or collagen polymerization and cross-linking. The application of micro- techniques in protein chemistry to tissue biopsies is the theme of the work. The goal with osteogenesis imperfecta is to understand better how a diversity of mutatiotis in type I collagen all result in brittle bone. By studying bone tissue (surgery and autopsy) from patients of known molecular defect, the degree to which mutations are expressed and persist extracellularly in cross-linked bone matrix will be examined. Is the disease principally one of collagen underproduction rather than the consequences of structurally inadequate collagen molecules forming the matrix? Likewise, the consequences of structural mutations and post-translational defects of collagen in Ehlers-Danlos syndromes VI ind VII will be defined in more detail. Efforts will be made to reveal inherited structural defects in cartilage-specific collagens (types II and IX) as the cause of curtain forms of chondrodystrophy, including the broadly-defined spondyloepiphyseal dysplasias and diastrophic dysplasias. The possibility that polymorphisms of the human type II collagen gene exist in the population, and perhaps account for observed natural variations in degree of cross-linking in human cartilage collagen, will be tested. Inherited mutations of type II collagen affecting cross-linking as a cause of familial osteoarthrosis will also be examined. The objective is to learn the importance of certain features of collagen structure, for example those that control cross-linking reactions, in determining function. Through an understanding of the effects of rare inborn mutations, so the normal properties of collagens and their variations can be better appreciated.