Ⅰ型先天性厚甲症K6a基因新突变的发现.docxVIP

安徽医科大学硕士擘住论文 Abstract Identification of a novel mutation in the K6a gene of Pachyonychia congenita type 1 Background Pachyonychia congenita(PC)is an autosomal dominant disorder that usually develops in early infancy．The major features of the syndrome are hypertrophic nail dystrophy，palmoplantar keratoderma and oral leueokeratosis，accompanied by other ectodermal defects，according to subtype．Specifically，PC一1 has been shown to be caused by mutations in keratins K6a and K16．In contrast，PC·2 has been associated with mutations in K6b and K17．K6／K16 ale co—expressed in a number ofdiffemntiated epithelial structures，including palmoplantar epidermis，mucosal epithelia,follicular keratinocytes and nail bed；whereas K17 is expressed in the pilosebaceous unit and basal appendageal keratinoeytes．To date，over 20 mutations in the K6a and KI 6 gene have been identified，the majority of these mutations are missense mutations． Comparison between genotype and phenotype failed to yield any clear correlation between the natnre of the mutation and the clinical features of PC．In the present study， we have ascertained an Chinese patient with PC-1，and examined the K6a and K16 genes mutation by direct sequencing． objeetive To analyze the K6a gene mutation in a sporadic Chinese patient with PC-1 and to explore the relationship between the genetype and phenotype of PC-1． Methods Genomic DNA Was extracted from peripheral blood ofthe patient with PC-1 and 100 unrelated normal persons．The whole coding region of the K6a gene was amplified using long-range polymerase chain reaction(PCR)，then nested PCR were used to amphfy the mutation‘hot-spot’of the K6a gene．The PCR products were directly sequenced to detect the mutation． ．S． 安徽医科大学硕士学位论文 Result A novel missense mutation L468Q in the helix 2B domain of the K6a polypeptide was identified in the patient but not in the healthy individuals from family and 100 unrelated nolmalindividuals． Conclusion We described this mutation for the