The Skeletal Dysplasias

骨骼发育不良

• 批准号: 7931042
• 负责人: DAVID L RIMOIN
• 金额: $ 5.06万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7931042
• 关键词: Skeletal; Dysplasias

DESCRIPTION (provided by applicant): The skeletal dysplasias are a group of more than 370 disorders that result in disproportionate short stature and/or skeletal deformities. Although they have long been considered to be generalized disorders of endochondral and/or membranous ossification, the extent of their heterogeneity and genetic basis is still being elucidated and their pathogenesis can now be investigated. This program project is directed toward a multidisciplinary investigation of the clinical, genetic, morphologic, biochemical, and molecular characteristics of the skeletal dysplasias. Specific aims include: 1. Expansion of the materials for study in the International Skeletal Dysplasia Registry. 2. Definition of the clinical and radiographic features and genetic heterogeneity of the skeletal dysplasias and elucidation of the natural history, growth characteristics, and complications of each of these disorders. 3. Improvement of methods for the antenatal diagnosis of prenatal-onset skeletal dysplasias. 4. Elucidation of the histological, histochemical, immunohistological, and ultrastructural characteristics of chondroosseous tissue in each of the skeletal dysplasias. 5. Identification of the disease genes in osteochondrodysplasias of unknown etiology, using linkage, positional cloning, and candidate gene approaches. 6. Correlation of the clinical, radiographic, and morphologic features of each skeletal dysplasia with their specific biochemical and molecular defects. 7. Development of a new Protein Biochemistry Core to provide specialized analytical methods, including protein mass spectrometry, to characterize the protein defects in human and mouse skeletal dysplasias. 8. Evaluation of the effects of post-translational modification of proteins on chondroosseous development. The program project is consisted of two core facilities, the International Skeletal Dysplasia Registry and the Protein Biochemistry Core, plus three integrated projects; (1) Clinical, pathophysiological and therapeutic studies; (2) Molecular studies in the skeletal dysplasias; and (3) Developmental studies in the skeletal dysplasias. The International Skeletal Dysplasia Registry, the largest such registry/database in the world, serves as an international resource for studying the skeletal dysplasias. A worldwide group of referring health professionals provide materials from clinically documented cases for these research projects are integrated to define a comprehensive understanding of the biological basis of these conditions.

描述（由申请方提供）：骨骼发育不良是一组超过370种导致不成比例身材矮小和/或骨骼畸形的疾病。虽然它们长期以来一直被认为是软骨内骨化和/或膜骨化的全身性疾病，但其异质性和遗传基础的程度仍在阐明，其发病机制现在可以研究。该项目旨在对骨骼发育不良的临床、遗传、形态、生化和分子特征进行多学科研究。具体目标包括：1.扩充国际骨发育不良登记研究资料。2.定义骨骼发育不良的临床和影像学特征和遗传异质性，并阐明每种疾病的自然史、生长特征和并发症。3.产前骨骼发育不良产前诊断方法的改进。4.阐明每种骨骼发育不良中软骨骨组织的组织学、组织化学、免疫组织学和超微结构特征。5.用连锁、定位克隆和候选基因方法鉴定病因不明的骨软骨发育不良的致病基因。6.每种骨骼发育不良的临床、影像学和形态学特征与其特定生化和分子缺陷的相关性。7.开发新的蛋白质生物化学核心，提供专门的分析方法，包括蛋白质质谱，以表征人类和小鼠骨骼发育不良中的蛋白质缺陷。8.蛋白质翻译后修饰对软骨骨发育影响的评价。该计划项目包括两个核心设施，国际骨骼发育不良登记处和蛋白质生物化学核心，加上三个综合项目：（1）临床，病理生理学和治疗研究;（2）骨骼发育不良的分子研究;和（3）骨骼发育不良的发育研究。国际骨骼发育不良登记处是世界上最大的此类登记处/数据库，是研究骨骼发育不良的国际资源。一个世界范围内的转介卫生专业人员提供的材料，从临床记录的情况下，这些研究项目被整合，以确定一个全面的了解这些条件的生物学基础。