MUTATIONS OF KERATIN-9 IN 2 FAMILIES WITH PALMOPLANTAR EPIDERMOLYTIC HYPERKERATOSIS

The hereditary palmoplantar keratodermas are a heterogeneous group of diseases unified by thickening of the stratum corneum of the palms and soles with consequent painful fissuring, discomfort on pressure, and resultant disability. One of the histologic patterns underlying palmop lantar hyperkeratosis is that of epidermolytic hyperkeratosis. Because that histologic pattern has been found in its generalized form to be due to keratin gene mutations, we assessed the inheritance of the form localized to the palms and soles. In each of two families studied, th e mutant gene causing the disease is linked strongly to the chromosome 17 cluster of genes encoding type I keratins, and mutations are prese nt in the conserved helix initiation region of keratin 9 in affected m embers of both kindreds. These data, as well as those generated recent ly by others, indicate that keratin gene mutations may underlie not on ly the generalized phenotype but also this more localized phenotype of epidermolytic hyperkeratosis and suggest one mechanism by which skin diseases can achieve their characteristic localization.