C1 INHIBITOR GENE AND HEREDITARY ANGIONEUROTIC EDEMA

这些研究的最终目标是精确地定义遗传 遗传性血管神经性水肿在分子水平上的缺陷 在 此外，正常和功能失调的完整结构的知识 C1抑制蛋白将有助于了解这种蛋白酶的功能 抑制剂. 这些研究可能会导致开发更具体的 遗传性血管神经性水肿的治疗，其产前检测， 最终应用于疾病的基因治疗。 为此，C1 已经分离出抑制剂cDNA克隆，并且正在对它们的序列进行测序。 测定 这将用于定义 蛋白 C1抑制因子基因的限制性片段长度多态性 将进行分析，并可能与Alport综合征的联系， 研究了 C1抑制剂的基因组克隆已被分离， 基因的结构将被确定。 基因组和cDNA文库 将由I型和II型遗传性 血管性水肿;将分离C1抑制剂克隆，并将其结构 确定并与正常值进行比较。 C1抑制剂的合成研究 通过体外单核细胞将有助于确定缺陷的水平， 最后，用编码正常和 功能失调的蛋白质将确定基因中可能的控制区域。

The ultimate goals of these studies are to precisely define the genetic defects, at the molecular level, in hereditary angioneurotic edema. In addition, knowledge of the complete structure of normal and dysfunctional C1 inhibitor proteins will help to understand the function of this protease inhibitor. These studies may lead to the development of more specific therapy for hereditary angioneurotic edema, to its prenatal detection and ultimately to gene therapy for the disease. Toward these ends, C1 inhibitor cDNA clones have been isolated, and their sequence is being determined. This will be used to define the complete sequence of the protein. Restriction fragment length polymorphism of the C1 inhibitor gene will be analyzed, and possible linkage to Alport's syndrome will be investigated. Genomic clones for C1 inhibitor have been isolated and the structure of the gene will be determined. Both genomic and cDNA libraries will be constructed from patients with type I and type II hereditary angioedemia; C1 inhibitor clones will be isolated and their structure determined and compared with the normal. Synthesis studies of C1 inhibitor by monocytes in vitro will help to define the level of the defects, and eventually transfection studies with genes coding for the normal and dysfunctional proteins will define possible control regions in the gene.