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.

Identification of novel and known KRT5 and KRT14 mutations in 53 patients with epidermolysis bullosa simplex: correlation between genotype and phenotype.

BACKGROUND: Basal epidermolysis bullosa simplex (EBS) is a hereditary skin blistering disorder resulting in most cases from missense mutations in the keratin 5 (KRT5) or keratin 14 (KRT14) genes. OBJECTIVES: To identify the underlying mutations in different EBS subtypes and correlate genotype and phenotype. METHODS: Mutation analysis was performed in 53 patients with EBS and their families by direct sequencing of the KRT5 and KRT14 genes. RESULTS: We identified 39 different mutations, of which 15 have not been published previously. Three novel deletion/insertion mutations, among them one in-frame duplication, were associated with the rare phenotype of EBS with mottled pigmentation. We identified for the first time a patient with compound heterozygosity for KRT5 mutations causing Dowling-Degos disease and EBS. CONCLUSIONS: Identification of novel mutations and genotype-phenotype correlations in EBS allow improved understanding of disease pathogenesis as well as better patient management.