Phenotypic heterogeneity in bullous congenital ichthyosiform erythroderma: possible somatic mosaicism for keratin gene mutation in the mildly affected mother of the proband.

BACKGROUND: Bullous congenital ichthyosiform erythroderma (BCIE) shows phenotypic variability. An epidermal nevus may represent somatic mosaicism for keratin gene mutation, which produces generalized BCIE in the next generation. This fact provides evidence that a postzygotic mutation can be passed on to the next generation in BCIE. We hypothesized that the same phenomenon occurred in a family with BCIE whose phenotypes were extremely different. OBSERVATIONS: We studied a 19-year-old boy with severe ichthyosiform erythroderma and prominent palmoplantar hyperkeratosis with digital contracture. In contrast, the proband's mother exhibited only mild ichthyosiform skin, granular verrucous lesions, and less severe streaky palmoplantar hyperkeratosis. Mutation analysis in the proband showed a keratin K1 mutation (N187S, ie, an A-to-G transition at the second position of codon 187, resulting in an asparagine-to-serine substitution). In the mother, the same keratin gene mutation was recognized, but only faintly in the leukocyte DNA, indicating that the amount of the mutated allele in leukocyte DNA was very low compared with that from the proband.
CONCLUSIONS: We speculate that the mildly affected mother showed keratin 1 gene mosaicism, and that the BCIE phenotype had been transmitted in a severe form through a mechanism that passes the keratin gene mutation to the next generation. These results suggest that mild forms of BCIE may actually represent extensive epidermal nevi/keratin gene mosaicism.