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Nat Genet. 2013 Oct;45(10):1244-1248. doi: 10.1038/ng.2739. Epub 2013 Aug 25.

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

Author information

1
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
2
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
3
Department of Cell Research and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
4
Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
5
Department of Cell and Developmental Biology, Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
6
Department of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
7
Department of Dermatology, Rambam Health Care Campus, Haifa, Israel.
8
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
9
Institute of Human Genetics, Haemek Medical Center, Afula, Israel.
10
Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
11
Pediatric Department B, Haemek Medical Center, Afula, Israel.
12
Pediatric Gastroenterology Unit, Haemek Medical Center, Afula, Israel.
13
Centre for Dermatology and Genetic Medicine, University of Dundee, Dundee, UK.
14
Division of Genetics and Molecular Medicine, King's College London (Guy's Campus), London, UK.
15
Paediatric Dermatology, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
16
National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
17
Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
18
St John's Institute of Dermatology, King's College London (Guy's Campus), London, UK.
19
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
#
Contributed equally

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.

PMID:
23974871
PMCID:
PMC3791825
DOI:
10.1038/ng.2739
[Indexed for MEDLINE]
Free PMC Article

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