New mutations in keratin 1 that cause bullous congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens

The intermediate filaments of epithelial cells are formed by keratins, a fa mily of structurally related proteins, which are expressed in pairs of acid ic (type I) and basic (type II) polypeptides in a tissue-and differentiatio n-specific manner. Mutations in the genes encoding several keratins have be en implicated in the pathogenesis of diseases of keratinization. We report molecular analysis of two patients with the rare autosomal dominant disorde rs bullous congenital ichthyosiform. erythroderma (BCIE) and ichthyosis bul losa of Siemens (IBS). Previous studies have shown that these genodermatose s are due to mutations in the KRT1 and KRT2E genes, respectively. We report a new amino acid substitution mutation in codon 155 of KRT1 (valine to asp artic acid) in the conserved HI domain of the protein in the patient with B CIE. We also report a novel amino acid substitution mutation in codon 192 o f KRT2E (asparagine to lysine) in the conserved 1A helix initiation peptide of the protein in the patient with IBS. Our results demonstrate that these mutations are deleterious to keratin filament network stability and lead t o specific clinical inherited disorders of keratinization.