MOLECULAR ANALYSIS OF COLLAGENS IN THE CHONDRODYSPLASIAS

本项目建议调查缺陷的作用， 软骨发育不良中的软骨胶原。 软骨发育不良是临床上常见的结缔组织疾病 由不成比例的矮小身材和骨骼异常所定义。 严重程度从轻微到致命不等，骨关节炎是一种常见的 许多这些疾病的特征。 第二类缺陷 胶原基因（COL2A1）在少数病例中被表征， 脊椎骨骺发育不良（SED），软骨发育不全II，和 软骨发育不良，遗传连锁分析表明， Stickler综合征患者某些激酶的COL2A1缺陷 （遗传性骨关节病）和常染色体显性遗传 骨关节炎 我们假设，在其他缺陷 软骨特异性胶原基因是额外的 软骨发育不良 该提案的目标是1）进一步表征突变 在COL2A1中，负责上述疾病，2） 将突变的位置和性质与临床 表型，以及3）开发和实施分子工具， 确定其他软骨特异性缺陷的作用 胶原蛋白 为了实现这些目标，将分析来自 SED、软骨发育不全和软骨发育不良患者，使用 现代分子技术。 研究对方的角色 软骨特异性胶原（IX、X和Xi型），DNA 这些基因的多态性将被开发，以促进 在Stickler家族中测试这些位点作为“候选基因” 综合征、多发性骨骺发育不良和类似疾病。 了解产生这些疾病的分子缺陷 应该澄清疾病的染色体位置， 确定其他胶原蛋白中突变的贡献 遗传性结缔组织疾病的基因。

This project proposes to investigate the role of defects in cartilage collagens in the chondrodysplasias. The chondrodysplasias are disorders of connective tissue clinically defined by disproportionate short stature and skeletal anomalies. Severity ranges from mild to lethal, and osteoarthritis is a common feature of many of these disorders. Defects in the type II collagen gene (COL2Al) have been characterized in a few cases of spondyloepiphyseal dysplasia (SED), achondrogenesis II, and hypochondrogenesis, and genetic linkage analysis has implicated defects in COL2A1 in some kindreds with Stickler syndrome (hereditary osteoarthropathy) and autosomal dominant osteoarthritis. We hypothesize that defects in other cartilage-specific collagen genes underlie additional chondrodysplasias. The goals of this proposal are 1) to further characterize mutations in COL2Al responsible for the disorders listed above, 2) to correlate the location and nature of the mutations with clinical phenotypes, and 3) to develop and implement molecular tools to determine the role of defects in other cartilage-specific collagens. To achieve these goals, cDNA will be analyzed from patients with SED, achondrogenesis, and hypochondrogenesis, using current molecular techniques. To study the roles of the other cartilage-specific collagens (types IX, X, and XI), DNA polymorphisms for these genes will be developed to facilitate testing these loci as "candidate genes" in families with Stickler syndrome, multiple epiphyseal dysplasia, and similar disorders. Understanding the molecular defects that produce these diseases should clarify the chromosomal locations of the disorders and determine the contribution of mutations in additional collagen genes to heritable disorders of connective tissue.