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

L Samuelov, O Sarig, RM Harmon, D Rapaport… - Nature …, 2013 - nature.com
L Samuelov, O Sarig, RM Harmon, D Rapaport, A Ishida-Yamamoto, O Isakov, JL Koetsier…
Nature genetics, 2013nature.com
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 …
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.
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