MUTATIONS IN THE ROD 1A DOMAIN OF KERATIN-1 AND KERATIN-10 IN BULLOUSCONGENITAL ICHTHYOSIFORM ERYTHRODERMA (BCIE)

Bullous congenital ichthyosiform erythroderma is a human hereditary sk in 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 w ith this disease. Two of these are in the helix 1A subdomain of the ty pe II keratin 1, giving a serine-to-proline substitution in codon 185 and an asparagine-to-serine substitution in codon 187. In the analogou s region of type I keratin 10, an arginine-to-proline and an arginine- to-serine transition in codon 156 have been identified. All four mutat ions create restriction fragment length polymorphisms that were used e xclude the mutations from 120 normal chromosomes. Insertional polymorp hism (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.