Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Ostrovityanova 1, 117997 Moscow, Russia.
Koltzov Institute of Developmental Biology of Russian Academy of Sciences, 26 Vavilova Str., 119334 Moscow, Russia.
Int J Mol Sci. 2021 Feb 11;22(4):1792. doi: 10.3390/ijms22041792.
The recessive form of dystrophic epidermolysis bullosa (RDEB) is a debilitating disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Mutations in the COL7A1 gene induce multiple abnormalities, including chronic inflammation and profibrotic changes in the skin. However, the correlations between the specific mutations in COL7A1 and their phenotypic output remain largely unexplored. The mutations in the COL7A1 gene, described here, were found in the DEB register. Among them, two homozygous mutations and two cases of compound heterozygous mutations were identified. We created the panel of primary patient-specific RDEB fibroblast lines (FEB) and compared it with control fibroblasts from healthy donors (FHC). The set of morphological features and the contraction capacity of the cells distinguished FEB from FHC. We also report the relationships between the mutations and several phenotypic traits of the FEB. Based on the analysis of the available RNA-seq data of RDEB fibroblasts, we performed an RT-qPCR gene expression analysis of our cell lines, confirming the differential status of multiple genes while uncovering the new ones. We anticipate that our panels of cell lines will be useful not only for studying RDEB signatures but also for investigating the overall mechanisms involved in disease progression.
隐性营养不良型大疱性表皮松解症（RDEB）是一种衰弱性疾病，由真皮和表皮基底膜连接处的缺陷引起。COL7A1 基因突变可引起多种异常，包括皮肤的慢性炎症和纤维母细胞增生性改变。然而，COL7A1 基因中的特定突变与其表型表现之间的相关性在很大程度上仍未得到探索。这里描述的 COL7A1 基因突变是在 DEB 登记处发现的。其中，鉴定出两个纯合突变和两个复合杂合突变病例。我们创建了一组原发性患者特异性 RDEB 成纤维细胞系（FEB），并将其与来自健康供体的对照成纤维细胞（FHC）进行了比较。细胞的形态特征和收缩能力将 FEB 与 FHC 区分开来。我们还报告了突变与 FEB 的几种表型特征之间的关系。基于 RDEB 成纤维细胞的可用 RNA-seq 数据分析，我们对我们的细胞系进行了 RT-qPCR 基因表达分析，证实了多个基因的差异状态，同时揭示了新的基因。我们预计，我们的细胞系面板不仅将有助于研究 RDEB 特征，而且有助于研究疾病进展中涉及的整体机制。
