Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

作者：Samuelov Liat; Sarig Ofer; Harmon Robert M; Rapaport Debora; Ishida Yamamoto Akemi; Isakov Ofer; Koetsier Jennifer L; Gat Andrea; Goldberg Ilan; Bergman Reuven; Spiegel Ronen; Eytan Ori; Geller Shamir; Peleg Sarit; Shomron Noam; Goh Christabelle S M; Wilson Neil J; Smith Frances J D; Pohler Elizabeth; Simpson Michael A; McLean W H Irwin; Irvine Alan D; Horowitz Mia; McGrath John A; Green Kathleen J; Sprecher Eli^*

来源：Nature Genetics, 2013, 45(10): 1244-U201.

DOI：10.1038/ng.2739

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.

• 出版日期2013-10
• 单位西北大学