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Abstract：
Keratinopathic ichthyoses (KI) are a clinically heterogeneous group of keratinization disorders due to mutations in KRT1, KTR10, or KRT2 genes encoding keratins of suprabasal epidermis. Characteristic clinical features include superficial blisters and erosions in infancy and progressive development of hyperkeratosis. Histopathology shows epidermolytic hyperkeratosis. We describe the clinical, histopathological, and molecular findings of a series of 26 Italian patients from 19 unrelated families affected with (i) epidermolytic ichthyosis due to KRT1 or KRT10 mutations (7 and 9 cases, respectively); (ii) KTR10-mutated ichthyosis with confetti (2 cases); (iii) KRT2-mutated superficial epidermolytic ichthyosis (5 cases); and (iv) KRT10-mutated epidermolytic nevus (2 cases). Of note, molecular genetic testing in a third case of extensive epidermolytic nevus revealed a somatic missense mutation (p.Asn186Asp) in the KRT2 gene, detected in DNA from lesional skin at an allelic frequency of 25% and, at very low frequency (1.5%), also in blood. Finally, we report three novel dominant mutations, including a frameshift mutation altering the C-terminal V2 domain of keratin 1 in three familiar cases presenting a mild phenotype. Overall, our findings expand the phenotypic and molecular spectrum of KI and show for the first time that epidermolytic nevus can be due to somatic KRT2 mutation.
摘要：
角质形成病性鱼鳞病（KI）是一组临床上异质的角质化疾病，这是由于编码上表皮角蛋白的KRT1，KTR10或KRT2基因突变所致。特征性临床特征包括婴儿期的浅表水疱和糜烂以及角化过度的进行性发展。组织病理学显示表皮角化过度。我们描述了临床，组织病理学,以及来自19个无关家庭的26名意大利患者的分子发现，这些患者患有（i）由于KRT1或KRT10突变而导致的表皮性鱼鳞病（7例和9例，分别）；（ii）KTR10突变的鱼鳞病伴五彩纸屑（2例）；（iii）KRT2突变的浅表表皮性鱼鳞病（5例）；（iv）KRT10突变的表皮性痣（2例）。值得注意的是，在第三例广泛的表皮痣中进行的分子遗传学测试显示出体细胞错义突变（p.Asn186Asp）在KRT2基因中，在病变皮肤的DNA中以25%的等位基因频率检测到，在非常低的频率（1.5％），也在血液中。最后,我们报告了三个新的显性突变，包括在三个常见病例中改变角蛋白1的C端V2结构域的移码突变，表现为轻度表型。总的来说,我们的研究结果扩展了KI的表型和分子谱,并首次显示表皮性痣可能是由于KRT2体细胞突变所致.
