Kosykh Anastasiya V, Ryumina Irina I, Botkina Alexandra S, Evtushenko Nadezhda A, Zhigmitova Elena B, Martynova Aleksandra A, Gurskaya Nadya G, Rebrikov Denis V
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Ostrovityanova 1, Moscow 117997, Russia.
National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V. I. Kulakov, ul Akademika Oparina, 4, Moscow 117997, Russia.
Int J Mol Sci. 2024 Mar 4;25(5):2989. doi: 10.3390/ijms25052989.
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 gene, and indirect effects via pathogenic mutation in the 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.
单纯性大疱性表皮松解症（EBS）是一种皮肤病，其特征为皮肤脆弱和水疱形成，这是由表皮基底层内的分离所致，可归因于多种遗传病因。本研究报告了幼儿中的三种新生致病性变异，临床表现最早出现在新生儿期。这些变异通过两种不同机制导致EBS表型：一种是由于基因中的致病性变异导致角蛋白直接异常，另一种是通过基因中的致病突变产生间接影响，该突变干扰了KRT14自然的蛋白酶体介导的降解途径。我们报告了一例严重的EBS病例，其斑驳色素沉着由KRT14中的Met119Thr致病性变异引起，另一例涉及致病性KLHL24 Met1Val变异，第三例以KRT14中的热点突变Arg125His为特征，所有病例均在出生后的头几周内出现。本研究强调了EBS中遗传影响的复杂性，并突出了早期基因筛查对准确诊断和管理的重要性。
