A GLUTAMATE TO LYSINE MUTATION AT THE END OF 2B ROD DOMAIN OF KERATIN2E GENE IN ICHTHYOSIS BULLOSA OF SIEMENS

lchthyosis bullosa of Siemens is a rare autosomal dominant skin disord er whose clinical findings are quite similar to those of epidermolytic hyperkeratosis. The differences between those two diseases include ab sence of erythroderma and different distributions in the shin in ichth yosis bullosa of Siemens. Recent studies have confirmed that ichthyosi s bullosa of Siemens is caused by the mutation in the keratin 2e (K2e) gene, which is expressed in the upper spinous and granular layers. We have identified a sporadic case of ichthyosis bullosa of Siemens; bas ed on diagnosis by histopathological findings, the K2e gene of the pat ient was analysed. Direct sequencing of PCR products revealed a single base change in sequences encoding the highly conserved end of the 2B rod domain segment of the K2e gene. This mutation results in substitut ion of the codon for glutamic acid by a codon for lysine in position 4 93 in K2e (E493K). Mutations of the K2e gene involving five different residue positions (Q187P, T485P, L490P, E493D, E493K and E494K) are kn own to cause ichthyosis bullosa of Siemens. Of these sites, E493, whic h is conserved in type I and type II keratin genes, is the most freque ntly altered amino acid in the K2e gene. These data together suggest t hat this codon constitutes a hot spot for mutations in the K2e gene.