title: Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting.
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.
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Liat
authors: L
authors: Samuelov
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Ofer
authors: O
authors: Sarig
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors: Robert M
authors: RM
authors: Harmon
authors: Department of Cell Research and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors: Debora
authors: D
authors: Rapaport
authors: Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
authors: Akemi
authors: A
authors: Ishida-Yamamoto
authors: Department of Cell and Developmental Biology, Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
authors: Ofer
authors: O
authors: Isakov
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors: Jennifer L
authors: JL
authors: Koetsier
authors: Department of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Andrea
authors: A
authors: Gat
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Ilan
authors: I
authors: Goldberg
authors: Department of Dermatology, Rambam Health Care Campus, Haifa, Israel.|Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors: Reuven
authors: R
authors: Bergman
authors: Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Institute of Human Genetics, Haemek Medical Center, Afula, Israel.
authors: Ronen
authors: R
authors: Spiegel
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.|Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors: Ori
authors: O
authors: Eytan
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Shamir
authors: S
authors: Geller
authors: Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Pediatric Department B, Haemek Medical Center, Afula, Israel.|Pediatric Gastroenterology Unit, Haemek Medical Center, Afula, Israel.
authors: Sarit
authors: S
authors: Peleg
authors: Department of Cell and Developmental Biology, Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.
authors: Noam
authors: N
authors: Shomron
authors: Centre for Dermatology and Genetic Medicine, University of Dundee, Dundee, UK.
authors: Christabelle S M
authors: CSM
authors: Goh
authors: Centre for Dermatology and Genetic Medicine, University of Dundee, Dundee, UK.
authors: Neil J
authors: NJ
authors: Wilson
authors: Centre for Dermatology and Genetic Medicine, University of Dundee, Dundee, UK.
authors: Frances J D
authors: FJD
authors: Smith
authors: Centre for Dermatology and Genetic Medicine, University of Dundee, Dundee, UK.
authors: Elizabeth
authors: E
authors: Pohler
authors: Division of Genetics and Molecular Medicine, King's College London (Guy's Campus), London, UK.
authors: Michael A
authors: MA
authors: Simpson
authors: Centre for Dermatology and Genetic Medicine, University of Dundee, Dundee, UK.
authors: W H Irwin
authors: WHI
authors: McLean
authors: Paediatric Dermatology, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.|National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.|Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
authors: Alan D
authors: AD
authors: Irvine
authors: Department of Cell Research and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors: Mia
authors: M
authors: Horowitz
authors: St John's Institute of Dermatology, King's College London (Guy's Campus), London, UK.
authors: John A
authors: JA
authors: McGrath
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.|Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors: Kathleen J
authors: KJ
authors: Green
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.|Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors: Eli
authors: E
authors: Sprecher
mesh_terms: D002648:Child; D002675:Child, Preschool; D003872:Dermatitis / Q000235:genetics*; D051183:Desmoglein 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation; D012720:Severity of Illness Index; D013577:Syndrome; D019282:Wasting Syndrome / Q000235:genetics* / Q000378:metabolism
chemical_list: D051183:Desmoglein 1
references: J Dermatol. 2011 Jul;38(7):645-54
references: 21545505
references: J Biol Chem. 2006 Feb 10;281(6):3614-24
references: 16286477
references: Br J Dermatol. 2012 Jan;166(1):36-45
references: 21929534
references: Allergol Int. 2012 Mar;61(1):27-34
references: 22270069
references: J Am Acad Dermatol. 2010 Jan;62(1):107-113
references: 20082890
references: J Pediatr. 2004 Jul;145(1):82-92
references: 15238912
references: Nat Genet. 2000 Jun;25(2):141-2
references: 10835624
references: Nat Methods. 2010 Apr;7(4):248-9
references: 20354512
references: Int J Pharm. 2012 Oct 1;435(1):3-9
references: 22705878
references: J Clin Invest. 2012 Feb;122(2):440-7
references: 22293182
references: Clin Exp Immunol. 2008 Sep;153 Suppl 1:27-9
references: 18721326
references: J Invest Dermatol. 1985 Jul;85(1 Suppl):161s-164s
references: 2409183
references: J Invest Dermatol. 2012 Mar;132(3 Pt 2):776-84
references: 22189787
references: Nat Rev Mol Cell Biol. 2011 Aug 23;12(9):565-80
references: 21860392
references: Am J Hum Genet. 2010 Aug 13;87(2):274-81
references: 20691404
references: Bioinformatics. 2010 Mar 1;26(5):589-95
references: 20080505
references: J Pediatr Gastroenterol Nutr. 2004 Feb;38(2):164-9
references: 14734878
references: Dermatology. 2006;212(2):117-22
references: 16484817
references: Genome Res. 2010 Sep;20(9):1297-303
references: 20644199
references: Nat Genet. 2007 May;39(5):650-4
references: 17417636
references: Science. 2011 Dec 2;334(6060):1293-7
references: 22144628
references: J Invest Dermatol. 2013 Jan;133(1):154-63
references: 22832486
references: Clin Exp Dermatol. 2009 Mar;34(2):224-8
references: 19018793
references: Hum Mol Genet. 1999 Jun;8(6):971-6
references: 10332028
references: J Invest Dermatol. 1996 Oct;107(4):539-42
references: 8823357
references: Nat Genet. 2005 Jan;37(1):56-65
references: 15619623
references: J Am Acad Dermatol. 2010 Oct;63(4):607-41
references: 20643494
references: J Cell Biol. 2009 Jun 29;185(7):1243-58
references: 19546243
references: J Clin Invest. 2010 Mar;120(3):871-82
references: 20179351
references: Arch Dermatol. 2005 May;141(5):625-8
references: 15897387
references: J Invest Dermatol. 2001 Aug;117(2):179-87
references: 11511292
references: Allergy. 2009 Dec;64(12):1758-65
references: 19839980
references: Cell Tissue Res. 2013 Feb;351(2):289-300
references: 23344365
references: Br J Dermatol. 2009 Oct;161(4):884-9
references: 19681860
references: J Invest Dermatol. 2006 Jul;126(7):1622-32
references: 16628198
references: J Cell Sci. 2009 Dec 15;122(Pt 24):4401-7
references: 19955337
references: Nat Protoc. 2009;4(7):1073-81
references: 19561590