CLINICAL, MORPHOLOGIC AND MOLECULAR STUDIES

描述(由申请人提供)： 骨骼发育不良是一个由200多种疾病组成的异质性群体。这 该项目旨在确定该病的临床、遗传学和病理学特征。 这些疾病，发展动物模型以更好地了解它们的 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性研究 其他项目和其他合作者。在支持期间，我们将： 1)对提交给国际骨骼协会的病例进行明确分类 异型增生登记处(核心A)，改善以前的特征 描述骨骼发育不良，并定义新的疾病；2)改善 骨骼发育不良的产前诊断方法；3)相互关联 不同骨骼的临床、X线和形态特征 有特定生化和分子缺陷的发育不良；4) 与子项目5、2、8和其他工作人员合作分析动物 用于鉴定人类同系物的软骨发育不良的验证 实验模型和对病理生理学的洞察；以及5)定位 利用连锁分析检测疾病基因座并鉴定其遗传缺陷 三种基本缺陷未知的骨骼发育不良，特别是 Desbuquis综合征，常染色体显性短小综合征，并与 面心肌骨骼综合征。

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.