Expanding the keratin mutation database: novel and recurrent mutations and genotype-phenotype correlations in 28 patients with epidermolytic ichthyosis

Background: Epidermolytic ichthyosis (EI) is a hereditary keratinization disorder caused by mutations in the keratin 1 (KRT1) or keratin 10 (KRT10) genes. In most cases of severe EI, heterozygous single point mutations are found at the highly conserved helix boundary motifs of KRT1 and KRT10 that play a critical role in filament formation. The presence of palmoplantar keratoderma suggests KRT1 mutations, whereas KRT10 mutations in most instances give rise to the nonpalmoplantar variants.

Objectives: To identify the underlying mutations in patients with EI and to correlate genotype and phenotype.

Methods: Mutation analysis was performed in 28 patients with EI by direct sequencing of KRT1 and KRT10 genes.

Results: We identified 14 different mutations, of which four have not been published previously.

Conclusions: Identification of novel mutations and genotype-phenotype correlations in EI allows improved understanding of disease pathogenesis as well as better patient management.