Mutations in the rod 1A domain of keratins 1 and 10 in bullous congenital ichthyosiform erythroderma (BCIE).

Bullous congenital ichthyosiform erythroderma is a human hereditary skin disorder in which suprabasal keratinocytes rupture. Recent reports have implicated keratins K1 and K10 in this disease. Here we describe four diverse keratin mutations that are all significantly associated with this disease. Two of these are in the helix 1A subdomain of the type II keratin 1, giving a serine-to-proline substitution in codon 185 and an asparagine-to-serine substitution in codon 187. In the analogous region of type I keratin 10, an arginine-to-proline and an arginine-to-serine transition in codon 156 have been identified. All four mutations create restriction fragment length polymorphisms that were used exclude the mutations from 120 normal chromosomes. Insertional polymorphism (in the V2 subdomains of the non-helical tails of K1 and K10) was excluded as the cause of the phenotypic heterogeneity observed within one family.