SEVERE PALMOPLANTAR HYPERKERATOSIS IN DOWLING-MEARA EPIDERMOLYSIS-BULLOSA SIMPLEX CAUSED BY A MUTATION IN THE KERATIN-14 GENE (KRT14)

Mutant keratins 5 or 14 are implicated in the etiology of epidermolysi s bullosa simplex (EBS), The catalog of mutations has established cert ain patterns of mutation clusters from which it may be possible, along with associated biochemical data, to predict phenotypic severity. It is becoming apparent that some of these assumptions may now require mo dification, We report a mutation in the gene encoding keratin 14 (KRT1 4) that changes the predicted amino acid at position 119, at the start of the helix initiation motif, from methionine to threonine (K14 M119 T) in a patient with an EBS Dowling-Meara phenotype with severe palmo- plantar hyperkeratosis, This demonstrates that the three major types o f EBS can arise front missense mutations in the same codon, The findin gs suggest that the specific nature of the missense mutation, in the c ontext of the protein sequence, can contribute far more to the clinica l severity than previously thought. The different EBS subtypes should be viewed as gradations of clinical severity rather than distinct gene tic diseases.