| Literature DB >> 23974871 |
Liat Samuelov1, Ofer Sarig1, Robert M Harmon2, Debora Rapaport3, Akemi Ishida-Yamamoto4, Ofer Isakov5, Jennifer L Koetsier2, Andrea Gat6, Ilan Goldberg1, Reuven Bergman7,8, Ronen Spiegel8,9, Ori Eytan1,10, Shamir Geller1, Sarit Peleg8,11,12, Noam Shomron5, Christabelle S M Goh13, Neil J Wilson13, Frances J D Smith13, Elizabeth Pohler13, Michael A Simpson14, W H Irwin McLean13, Alan D Irvine15,16,17, Mia Horowitz3, John A McGrath18, Kathleen J Green2,19, Eli Sprecher1,10.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2013 PMID： 23974871 PMCID： PMC3791825 DOI： 10.1038/ng.2739
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330