掌跖角化症一大家系突变基因的筛查定位及相应角蛋白功能的研究

Palmoplantar keratoderma (PPK ) is a group of clinical manifestations of diversity keratinized skin disease, with a high degree of genetic heterogeneity，characterized by palmoplantar skin thickening. The thick skin lesions can affect movement, and is also associated with cancer or heart disease syndrome. Hereditary palmoplantar keratoderma always appears as autosomal dominant inheritance. we intend to screen and locate the mutation loci in the large domestic family of epidermolytic palmoplantar keratoderma ( EPPK ), prepare the site-directed mutant cDNA to obtain the related keratin, and observe the changed function after expression. The present researches indicate that KRT9 mutation was the basis of the pathogenesis ,and KRT1 gene mutation accounting for several another small groups. Preliminary STR linkage analysis had excluded relation between the two genes with our EPPK family, calling for the whole genome scanning and further linkage analysis. So the incidence of detecting a new mutation loci is hopeful. Our research will enrich the genetic database resources in China, help to understand the related change in keratin , and provide a new idea for the the gene diagnosis, clinical treatment and the development of new drugs for EPPK .

掌跖角化病（palmoplantar keratodermas，PPK）是一组临床表现多样，具有高度遗传异质性的角化性皮肤病，以掌跖部角质增厚为特征，皮损可影响运动功能，并常合并肿瘤或心脏病等综合症。遗传性掌跖角化症多呈常染色体显性遗传，我们拟对收集到的目前国内最大的表皮松解性掌跖角化病（EPPK）家系进行突变基因的筛查与定位，同时通过定点突变获得相应角蛋白的突变cDNA，表达后研究其角蛋白的功能变化。国内外的研究表明EPPK的发病多由KRT9或KRT1基因突变导致，而本课题前期的STR连锁分析结果表明上述两个基因与该EPPK家系发病无相关性，预期进一步的全基因组扫描结合连锁分析发现新的致病基因的几率非常大。该研究将进一步丰富我国遗传数据库资源，有助于PPK致病基因及其相关角蛋白功能变化的研究，加深对PPK分子遗传机制的认识，从而为该病基因诊断、临床治疗及新药开发提供依据和新思路。