CLINICAL, MORPHOLOGIC AND MOLECULAR STUDIES

描述（申请人提供）： 骨骼发育不良是一组异质性的200多种疾病。这 该项目旨在确定临床，遗传和病理特征， 这些疾病，开发动物模型，以更好地了解他们的 发病机制，通过连锁确定三种疾病的分子缺陷 分析并进行临床分子相关研究， 其他项目和其他合作者。在支持期间，我们将： 1)对提交给国际刑事法院的案件进行最后分类 异型增生登记研究（核心A），改善先前的特征 描述骨骼发育不良，并定义新的疾病; 2）改善 用于骨骼发育不良的产前诊断的方法; 3）相关 不同骨骼的临床、影像学和形态学特征 发育不良及其特定的生化和分子缺陷; 4）在 与子项目5、2、8和其他工作人员合作，分析动物 软骨发育不良用于人类同源物鉴定的验证 实验模型，并深入了解病理生理学;和5）定位 利用连锁分析确定致病基因位点， 三种骨骼发育不良，其中基本缺陷未知，特别是 Desbuquois综合征、常染色体显性遗传性短肢畸形及相关 面心肌肉骨骼综合征

Description (provided by applicant): The skeletal dysplasias are a heterogeneous group of over 200 disorders. This project seeks to define the clinical and genetic and pathologic features of these disorders, develop animal models to better understand their pathogenesis, define the molecular defect in three disorders by linkage analysis and perform clinical molecular correlative studies with each of the other projects and other collaborators. During the period of support, we will: 1) definitively classify cases submitted to the International Skeletal Dysplasia Registry (Core A), improve the characterization of previously described skeletal dysplasias, and define novel disorders; 2) improve the methods used for prenatal diagnosis of the skeletal dysplasias; 3) correlate the clinical, radiographic, and morphological features of different skeletal dysplasias with their specific biochemical and molecular defects; 4) in collaboration with subprojects 5, 2, 8, and other workers analyze animal chondrodysplasias for identification of human homologues, validation of experimental models, and insight into the pathophysiology; and 5) localize the disease gene locus using linkage analysis and identify the genetic defect for three skeletal dysplasias where the basic defect is not known, specifically Desbuquois syndrome, autosomal dominant brachyolmia, and linked faciocardiomusculoskeletal syndrome.