Arginine in the beginning of the 1A rod domain of the keratin 10 gene is the hot spot for the mutation in epidermolytic hyperkeratosis

Keratin intermediate filaments are expressed in specific type I/type II pai rs in the stage of differentiation of keratinocytes. The mutations in the k eratin genes expressed in the epidermis are etiologically responsible for s everal epidermal genetic skin diseases, such as epidermolysis bullosa simpl ex, epidermolytic hyperkeratosis (EHK), ichthyosis bullosa of Siemens, palm oplantar keratoderma, pachyonchia congenita and white sponge nevus. The mut ations of keratins 1/10 which are expressed in spinous and granular layers are confirmed to cause EHK. There are several trials to correlate between t he clinical phenotypes and sites of mutations of the keratin genes. One of these is that EHK is divided into two groups: the palms and soles involveme nt (PS) group and the non-palms and soles (NPS) group. So far the PS group had the mutations in the keratin 1 and the NPS group in keratin 10. Most of the mutations of the NPS group were reported in the beginning of the 1A ro d domain and over 2/3 of the mutations in the 1A rod domain were the base p air substitution of arginine, Here we find two different mutations in two u nrelated Korean kindreds classified as NPS group-R156C and R156H-in the 1A rod domain of keratin 10. Our results are compatible with the above classif ication and suggest that the arginine in the beginning of the 1A rod domain is the hot spot for the mutation of the keratin 10 gene. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.