@article{c0e0a87dff2d4e0f8fed27651eb94047,
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.",
author = "Liat Samuelov and Ofer Sarig and Harmon, {Robert M.} and Debora Rapaport and Akemi Ishida-Yamamoto and Ofer Isakov and Koetsier, {Jennifer L.} and Andrea Gat and Ilan Goldberg and Reuven Bergman and Ronen Spiegel and Ori Eytan and Shamir Geller and Sarit Peleg and Noam Shomron and Goh, {Christabelle S.M.} and Wilson, {Neil J.} and Smith, {Frances J.D.} and Elizabeth Pohler and Simpson, {Michael A.} and McLean, {W. H.Irwin} and Irvine, {Alan D.} and Mia Horowitz and McGrath, {John A.} and Green, {Kathleen J.} and Eli Sprecher",
note = "Funding Information: We thank S. Getsios for the use of the Zeiss Apotome. We thank D. Garrod (University of Manchester) for the kind gift of 11-5F antibody to DSP. We thank K. Stone (King{\textquoteright}s College London) for technical assistance in whole-exome sequencing. This work was supported by a generous donation of the Ram family to E.S.; US National Institutes of Health (NIH) grant RO1 AR041836 and the Joseph L. Mayberry Senior Endowment to K.J.G.; JSPS (Japan Society for the Promotion of Science) Kakenhi grant 24591620 and a grant from the Ministry of Health, Labor and Welfare of Japan to A.I.-Y.; DebRA (Dystrophic Epidermolysis Bullosa Research Association) UK to J.A.M.; the Wellcome Trust (programme grant 092530/Z/10/Z to W.H.I.M. and A.D.I. and bioresources grant 090066/B/09/Z to A.D.I. and W.H.I.M.); the National Children{\textquoteright}s Research Centre to A.D.I.; and the Pachyonychia Congenita Project to F.J.D.S. Some control sections were obtained from the Pathology Core of the Northwestern University Skin Disease Research Center (NIH grant P30AR057216). The Centre for Dermatology and Genetic Medicine at the University of Dundee is supported by a Wellcome Trust Strategic Award (098439/Z/12/Z to W.H.I.M.). L.S. is the recipient of an Excellence Award from the Tel Aviv Sourasky Medical Center.",
year = "2013",
month = oct,
doi = "10.1038/ng.2739",
language = "אנגלית",
volume = "45",
pages = "1244--1248",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "10",
}