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.

Key words: Epidermolysis bullosa simplex, Keratin, Mutation