Dermatology and Genetic Medicine, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Pachyonychia Congenita Project, Holladay, UT, USA.
Clin Exp Dermatol. 2019 Jul;44(5):528-534. doi: 10.1111/ced.13800. Epub 2018 Oct 4.
Mutations in keratin genes underlie a variety of epidermal and nonepidermal cell-fragility disorders, and are the genetic basis of many inherited palmoplantar keratodermas (PPKs). Epidermolytic PPK (EPPK) is an autosomal dominant disorder that can be due to mutations in the keratin 1 gene, KRT1. Epidermolytic ichthyosis (EI), the major keratinopathic ichthyosis, is characterized by congenital erythroderma, blistering and erosions of the skin. Causative mutations in KRT1 and KRT10 have been described, with PPK being present primarily in association with the former. We report four unrelated cases (one with sporadic EI and three with autosomal dominant PPK), due to two novel and two recurrent KRT1 mutations. Mutations in KRT1 are not only scattered throughout the keratin 1 protein, as opposed to being clustered, but can result in a range of phenotypes as further confirmed by these mutations, giving a complex genotype/phenotype pattern.
角蛋白基因突变是多种表皮和非表皮细胞脆弱性疾病的基础，也是许多遗传性掌跖角化过度症（PPK）的遗传基础。表皮松解性掌跖角化过度症（EPPK）是一种常染色体显性遗传疾病，可由角蛋白 1 基因（KRT1）突变引起。表皮松解性鱼鳞病（EI）是主要的角蛋白病鱼鳞病，其特征为先天性红皮病、水疱和皮肤糜烂。KRT1 和 KRT10 的致病突变已被描述，主要与前者相关的 PPK 存在。我们报告了四个无关病例（一例散发性 EI 和三例常染色体显性 PPK），由两个新的和两个复发性 KRT1 突变引起。KRT1 中的突变不仅散布在整个角蛋白 1 蛋白中，而不是聚集在一起，而且正如这些突变进一步证实的那样，可导致一系列表型，从而产生复杂的基因型/表型模式。
