Mutations in genes encoding the keratin intermediate filaments expressed in 
basal cells have been identified in some families with epidermolysis bullosa 
simplex as the proximate cause of the fragility. We have systematically scanned 
genomic sequences of one of these keratins, keratin 14, for mutations in 
patients from 49 apparently independent kindreds using single-strand 
conformation polymorphism analysis. The ten mutations identified are clustered 
at three sites--the ends of the helices and the L12 linker region, mutation 
sites that have been identified in past, more limited studies. Early onset of 
blistering in these ten families is correlated with more widespread distribution 
of lesions.