A mutation in the V1 domain of K16 is responsible for unilateral palmoplantar verrucous nevus

Palmoplantar keratodermas are a group of heterogeneous diseases characteriz ed by thickening, and marked hyperkeratosis, of the epidermis of the palms and soles. Palmoplantar keratodermas can be divided into four major classes : diffuse, focal, punctate, and palmoplantar ectodermal dysplasias. All for ms are genetic diseases inherited as autosomal dominant disorders. We studi ed a patient exhibiting a localized thickening of the skin in parts of the right palm and the right sole, following Blaschko's lines, that does not fi t into any classes already described. We sequenced the keratin 16 cDNA deri ved from skin biopsy material from affected and non affected palms. The ker atin 16 cDNA sequence from lesional epidermis showed a 12 base pair deletio n (309-320del), which deletes codons 104-107. The mutation is predicted to delete four amino acids, GGFA, from the V1 domain of the keratin 16 polypep tide, close to the 1A domain. Full-length keratin 16 cDNA sequence derived from the unaffected palm was completely normal, consistent with a postzygot ic mutation as is suggested by the mosaicism observed. We defined this new clinical entity, ''unilateral palmoplantar verrucous nevus'', rather than l ocalized or focal epidermolytic palmoplantar keratodermas, as the lesions a re present only on one side of the body and follow Blaschko's lines. This s tudy is a report of a mosaic mutation in keratin 16 and also the associatio n of a mutation in the V1 domain of a type I keratin associated with a huma n disease.