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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

259 Scopus citations

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.

Original languageEnglish
Pages (from-to)1244-1248
Number of pages5
JournalNature Genetics
Volume45
Issue number10
DOIs
StatePublished - Oct 2013

Funding

FundersFunder number
Joseph L. Mayberry Senior Endowment
Ministry of Health, Labor and Welfare of Japan
National Children’s Research Centre
Pachyonychia Congenita Project098439/Z/12/Z
National Institutes of HealthRO1 AR041836
National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin DiseasesP30AR057216
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Dystrophic Epidermolysis Bullosa Research Association
Wellcome Trust090066/B/09/Z, 092530/Z/10/Z
Wellcome Trust
Japan Society for the Promotion of Science24591620
Japan Society for the Promotion of Science

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