PDF(Pubmed)
Abstract：
Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents three pathogenic de novo variants in young children, with clinical manifestations appearing as early as the neonatal period. The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the Krt14 gene, and indirect effects via pathogenic mutation in the KLHL24 gene, which interfere with the natural proteasome-mediated degradation pathway of KRT14. We report one severe case of EBS with mottled pigmentation arising from the Met119Thr pathogenic variant in KRT14, another case involving a pathogenic KLHL24 Met1Val variant, and a third case featuring the hot spot mutation Arg125His in KRT14, all manifesting within the first few weeks of life. This research underscores the complexity of genetic influences in EBS and highlights the importance of early genetic screening for accurate diagnosis and management.
摘要：
单纯大疱性表皮松解症（EBS）是一种皮肤病，其特征是由于表皮基底层内的分离而导致皮肤脆性和水疱形成。这可以归因于各种遗传病因。这项研究提出了幼儿的三种致病性从头变异，临床表现早在新生儿期出现。这些变体通过两种不同的机制促成EBS表型：由于Krt14基因中的致病变体导致的直接角蛋白异常，以及通过KLHL24基因致病突变的间接影响，干扰天然蛋白酶体介导的KRT14降解途径。我们报告了一例由KRT14中的Met119Thr致病性变异引起的斑驳色素沉着的EBS严重病例，另一例涉及致病性KLHL24Met1Val变异，第三个病例以KRT14的热点突变Arg125His为特征，所有病例都在生命的最初几周内出现。这项研究强调了EBS遗传影响的复杂性，并强调了早期遗传筛查对准确诊断和管理的重要性。
