家族性寒冷性荨麻疹新致病基因的鉴定及致病机制研究

荨麻疹发病率高、亚型与病因多样、发病机制不明、治疗上颇为棘手，家族性寒冷性荨麻疹为临床罕见的常染色体显性遗传性疾病,是寒冷性荨麻疹的一个特殊类型。以鄂尔多斯两个家族性寒冷性荨麻疹家系为基础，通过遗传学及生物信息学分析手段筛选SLC44A3、TRMT5基因新的致病突变位点，在基因组学、蛋白组学、动物模型、散发病例、正常人群等不同层次上鉴定SLC44A3、TRMT5基因的突变位点，阐明SLC44A3、TRMT5基因突变位点的致病分子机制，为致病基因的结构和功能的研究提供有益的线索；并通过构建体外细胞的表达载体和动物模型，确定SLC44A3、TRMT5基因突变位点对寒冷性荨麻疹发生的作用及其与相关蛋白质功能的关系，进一步验证氨基酸改变的致病分子机制；对于了解家族性寒冷性荨麻疹病因、明确寒冷性荨麻疹发病机制、遗传咨询及药物开发具有重要意义。

It is rather difficult with high incidence , diverse of subtypes and etiologies, unknown pathogenesis and treatment in urticaria. It is special type of the family cold urticaria, which is a rare autosomal dominant hereditary disease in the clinic. Based on two families of cold urticaria in Ordos, the new pathogenic mutation sites of slc44a3 and trmt5 genes were screened through genetic and bioinformatics analysis. The mutation sites of slc44a3 and trmt5 genes were identified at different levels of genomics, proteomics, animal models, sporadic cases and normal people, and the mutation sites of slc44a3 and trmt5 genes were clarified It can provide useful clues about molecular mechanism of trmt5 gene mutation in study of the structure and function of the pathogenic genes. The slc44a3 can be determined by constructing the expression vector and animal model in vitro . The  relationship between trmt5 gene mutation and related protein function of cold urticaria , further verify the pathogenic molecular mechanism of amino acid change, which is of great significance for understanding the cause of familial cold urticaria, clarifying the pathogenesis of cold urticaria, genetic consultation and drug development.