Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Nat Genet. 2013 Oct;45(10):1244-1248. doi: 10.1038/ng.2739. Epub 2013 Aug 25.
The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and have a crucial role in maintaining epidermal integrity and barrier function. Mutations causing SAM syndrome resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. Our deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.
免疫失调和上皮屏障功能受损对过敏性疾病的相对贡献仍存在争议。在这里，我们描述了一种新的综合征，其特征为严重的皮炎、多种过敏和代谢消耗（SAM 综合征），由 DSG1 中的纯合突变引起。DSG1 编码桥粒芯糖蛋白 1，是桥粒的主要成分，桥粒将细胞表面与角蛋白细胞骨架连接，并在维持表皮完整性和屏障功能方面发挥关键作用。导致 SAM 综合征的突变导致 DSG1 缺乏膜表达，导致细胞-细胞黏附丧失。此外，DSG1 缺乏与编码过敏相关细胞因子的许多基因的表达增加有关。我们对 SAM 综合征发病机制的破译证实了这样一种观点，即过敏可能源于表皮的主要结构缺陷。
