A NEW KERATIN 2E MUTATION IN ICHTHYOSIS BULLOSA OF SIEMENS

Ichthyosis bullosa of Siemens (IBS) is a rare autosomal dominant skin condition with features similar to epidermolytic hyperkeratosis (EH). Clinical symptoms are characterized by mild hyperkeratosis with an acr al distribution, Histology shows epidermolysis of upper spinous and gr anular cells, whereas ultrastructurally, tonofilaments form perinuclea r aggregates, IBS has been linked to the type LT keratin cluster on ch romosome 12q, and K2e mutations have recently been identified in IBS p atients. We have studied genomic DNA from two IBS families and in both cases heterozygous point mutations were found in the 2B helical domai n. of K2e. One family had an established mutation in codon 493 (E493K) , whereas the other had an unreported mutation. in the adjacent codon (E494K). Both mutations were confirmed by allele-specific PCR, These d ata reinforce the hypothesis that mutations in the TYRKLLEGEE motif of the 2B helix are deleterious to keratin filament network integrity an d provide further evidence for the involvement of K2e mutations In IBS .