PATHOLOGY OF INBORN SKELETAL DISEASES

胶原蛋白结构中的先天性分子缺陷正在被表征 在各种骨骼疾病中。重点是骨生成 Ehlers Danlos综合征和某些软骨营养不良。的 特别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作用， 胶原聚合和交联。微电子的应用 技术在蛋白质化学组织活检是主题， 工作 成骨细胞学的目标是更好地理解 I型胶原的变异多样性均导致骨质疏松。 通过研究骨组织（手术和尸检）从病人已知的 分子缺陷，突变表达的程度， 将检查在交联骨基质中的细胞外持久性。是 这种疾病主要是胶原蛋白生产不足，而不是 结构上不充分的胶原蛋白分子形成的后果， 矩阵？同样，结构突变和 Ehlers-Danlos综合征中胶原的翻译后缺陷VI ind VII将被更详细地定义。 将努力揭示遗传性结构缺陷， 软骨特异性胶原蛋白（II型和IX型）作为窗帘的原因 各种形式的软骨营养不良，包括广泛定义的 脊椎骨骺发育不良和畸形性发育不良。的 人II型胶原基因多态性存在的可能性 在人群中，也许可以解释观察到的自然变化 在人软骨胶原中的交联程度将被测试。 II型胶原蛋白的遗传突变影响交联， 也将检查家族性骨关节病的病因。 目的是了解胶原蛋白的某些特征的重要性 结构，例如那些控制交联反应的结构， 决定功能通过了解稀有的 先天突变，因此胶原蛋白的正常特性及其 可以更好地理解变化。

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.