Yang J M, Nam K, Kim S W, Jung S Y, Min H G, Yeo U C, Park K B, Lee J H, Suhr K B, Park J K, Lee E S
Department of Dermatology, College of Medicine, Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea.
J Dermatol Sci. 1999 Feb;19(2):126-33. doi: 10.1016/s0923-1811(98)00055-3.
Keratin intermediate filaments are expressed in specific type I/type II pairs in the stage of differentiation of keratinocytes. The mutations in the keratin genes expressed in the epidermis are etiologically responsible for several epidermal genetic skin diseases, such as epidermolysis bullosa simplex, epidermolytic hyperkeratosis (EHK), ichthyosis bullosa of Siemens, palmoplantar keratoderma, pachyonchia congenita and white sponge nevus. The mutations of keratins 1/10 which are expressed in spinous and granular layers are confirmed to cause EHK. There are several trials to correlate between the 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 involvement (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 rod domain and over 2/3 of the mutations in the 1A rod domain were the base pair substitution of arginine. Here we find two different mutations in two unrelated Korean kindreds classified as NPS group-R156C and R156H-in the 1A rod domain of keratin 10. Our results are compatible with the above classification 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.
角蛋白中间丝在角质形成细胞分化阶段以特定的I型/II型对形式表达。在表皮中表达的角蛋白基因突变在病因上导致了几种表皮遗传性皮肤病，如单纯性大疱性表皮松解症、表皮松解性角化过度（EHK）、西门子大疱性鱼鳞病、掌跖角化病、先天性厚甲症和白色海绵状痣。在棘层和颗粒层表达的角蛋白1/10突变被证实可导致EHK。有多项研究试图将角蛋白基因的临床表型与突变位点联系起来。其中之一是将EHK分为两组：累及手掌和足底（PS）组和不累及手掌和足底（NPS）组。到目前为止，PS组在角蛋白1中存在突变，NPS组在角蛋白10中存在突变。NPS组的大多数突变报道于1A杆状结构域起始处，且1A杆状结构域中超过2/3的突变是精氨酸的碱基对替换。在此，我们在两个无关的韩国家系中发现了位于角蛋白10的1A杆状结构域中的两种不同突变，这两个家系被归类为NPS组——R156C和R156H。我们的结果与上述分类相符，并表明1A杆状结构域起始处的精氨酸是角蛋白10基因突变的热点。
