Background Ichthyosis vulgaris (IV) is a genetic disorder with a prevalence of 1 : 250- 1000 caused by filaggrin (FLG) mutations, which also predispose to atopic diseases.
Objectives To study the genotype/phenotype relationship in IV and to analyse whether the suggested skin barrier defect is associated with differences of epidermal dendritic cells.
Patients/methods We evaluated a cohort of 26 German patients with IV, established an IV severity score and analysed epidermal ultrastructure, histology, filaggrin and CD1a antigens. Mutations were screened by restriction enzyme analysis. Particular sequencing techniques allowed the complete FLG analysis to reveal novel mutations.
Results The combined null allele frequency of R501X and 2282del4 was 67.3%. Patients also showed the mutations S3247X and R2447X as well as five novel FLG mutations: 424del17 and 621del4 (profilaggrin S100 domain), 2974delGA (repeat 2), R3766X (repeat 10(1)) and E4265X (repeat 10(2)). Their combined allele frequency in controls was < 0.7%. No mutation was found in one IV patient, all in all similar to 27% were heterozygous, and the majority (similar to 69%) showed two null alleles. The IV severity score and ultrastructure showed a significant correlation with genotypes. Interestingly, CD1a cell counts showed a significant difference between nonatopic and atopic IV patients both with eczema and without eczema.
Conclusions We confirm that the mutations R501X and 2282del4 represent the most frequent genetic cause in German IV patients. The novel mutations are probably population and family specific. The observed differences of CD1a cells support the hypothesis that there is a barrier defect that predisposes to atopic manifestations, possibly independent of atopic eczema.
- dendritic cells
- epidermal barrier
- keratinisation disorders
- OF-FUNCTION MUTATIONS
- AUTOSOMAL DOMINANT ICHTHYOSIS
- FILAGGRIN GENE PREDISPOSE
- KERATOHYALIN GRANULES
- FUNCTION VARIANTS
- RARE MUTATIONS