【摘要】 目的鉴定更多的单纯型大疱性表皮松解症（EBS）突变以研究EBS基因型和表型关系，为EBS的遗传咨询及基因诊断和基因治疗奠定基础。方法应用聚合酶链反应、单链构象多态性和DNA直接测序明确基因突变位点和突变方式。结果家系Ⅰ用蛋白K14L12区存在V268D错义突变，家系Ⅱ角蛋白K5L12区存在N3295错义突变。结论进一步证明K5／K14的L12区是许多EBS－Weber－Cockayne突变定位的区域，K5／K14的L12区的多个位点的突变均可以引起EBS－Weber－Cockayne的发生。同时进一步证实了K5／K14的L12区对角蛋白装配不如其螺旋起始肋或螺旋终末肽重要，因而发生于K5／K14的L12区的突变仅能引起较轻的EBS－Weber－Cockayne亚型。更多还原

【Abstract】 Objective To identify additional epidermolysis bullosa simplex(EBS) mutations for studying the correlation between genotype and phenotype of EBS, and to provide hasis for genetic counselling, as well as for gene diagnosis and gene therapy. Methods PCR, SSCP, direct DNA sequeneing were employed to determine the mutation sites and mutation fashions. Results A V268D missense mutation within K14 L12domain was determined in family one, and a N329S missense mutation within K5 L12 domain was found in family two. Conclusion The results verify further that K5/K14 L12 domain is a preferred region within which many EBS-WC mutations are located. and mutations in several different residues of K5 /K14 L12 domain could lead to EBS-WC. The results also demonstrate that K5 /K14 L12 domain is not as important as K5/K14 HIP (helix initiation peptide)or HTP(helix termination peptide) for keratin intermediate filament assembly, so the mutations within L12 domain only lead to the milder EBS-WC subtype.[更多还原