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 acral distribution. Histology shows epidermolysis of upper spinous and granular cells, whereas ultrastructurally, tonofilaments form perinuclear aggregates. IBS has been linked to the type II keratin cluster on chromosome 12q, and K2e mutations have recently been identified in IBS patients. We have studied genomic DNA from two IBS families and in both cases heterozygous point mutations were found in the 2B helical domain 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 data reinforce the hypothesis that mutations in the TYRKLLEGEE motif of the 2B helix are deleterious to keratin filament network integrity and provide further evidence for the involvement of K2e mutations in IBS.