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

    Research output: Contribution to journalLetter

    148 Citations (Scopus)

    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
    JournalNature Genetics
    Early online date25 Aug 2013
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Desmoglein 1
    Dermatitis
    Hypersensitivity
    Wasting Syndrome
    Desmosomes
    Mutation
    Keratins
    Cytoskeleton
    Cell Adhesion
    Cytokines
    Membranes
    Genes

    Cite this

    Samuelov, L., Sarig, O., Harmon, R. M., Rapaport, D., Ishida-Yamamoto, A., Isakov, O., ... Sprecher, E. (2013). Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nature Genetics. https://doi.org/10.1038/ng.2739
    Samuelov, Liat ; Sarig, Ofer ; Harmon, Robert M. ; Rapaport, Debora ; Ishida-Yamamoto, Akemi ; Isakov, Ofer ; Koetsier, Jennifer L. ; Gat, Andrea ; Goldberg, Ilan ; Bergman, Reuven ; Spiegel, Ronen ; Eytan, Ori ; Geller, Shamir ; Peleg, Sarit ; Shomron, Noam ; Goh, Christabelle S. M. ; Wilson, Neil J. ; Smith, Frances J. D. ; Pohler, Elizabeth ; Simpson, Michael A. ; McLean, W. H. Irwin ; Irvine, Alan D. ; Horowitz, Mia ; McGrath, John A. ; Green, Kathleen J. ; Sprecher, Eli. / Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. In: Nature Genetics. 2013.
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    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",
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    Samuelov, L, Sarig, O, Harmon, RM, Rapaport, D, Ishida-Yamamoto, A, Isakov, O, Koetsier, JL, Gat, A, Goldberg, I, Bergman, R, Spiegel, R, Eytan, O, Geller, S, Peleg, S, Shomron, N, Goh, CSM, Wilson, NJ, Smith, FJD, Pohler, E, Simpson, MA, McLean, WHI, Irvine, AD, Horowitz, M, McGrath, JA, Green, KJ & Sprecher, E 2013, 'Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting', Nature Genetics. https://doi.org/10.1038/ng.2739

    Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. / Samuelov, Liat; Sarig, Ofer; Harmon, Robert M.; Rapaport, Debora; Ishida-Yamamoto, Akemi; Isakov, Ofer; Koetsier, Jennifer L.; Gat, Andrea; Goldberg, Ilan; Bergman, Reuven; Spiegel, Ronen; Eytan, Ori; Geller, Shamir; Peleg, Sarit; Shomron, Noam; Goh, Christabelle S. M.; Wilson, Neil J.; Smith, Frances J. D.; Pohler, Elizabeth; Simpson, Michael A.; McLean, W. H. Irwin; Irvine, Alan D.; Horowitz, Mia; McGrath, John A.; Green, Kathleen J.; Sprecher, Eli.

    In: Nature Genetics, 2013.

    Research output: Contribution to journalLetter

    TY - JOUR

    T1 - Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

    AU - Samuelov, Liat

    AU - Sarig, Ofer

    AU - Harmon, Robert M.

    AU - Rapaport, Debora

    AU - Ishida-Yamamoto, Akemi

    AU - Isakov, Ofer

    AU - Koetsier, Jennifer L.

    AU - Gat, Andrea

    AU - Goldberg, Ilan

    AU - Bergman, Reuven

    AU - Spiegel, Ronen

    AU - Eytan, Ori

    AU - Geller, Shamir

    AU - Peleg, Sarit

    AU - Shomron, Noam

    AU - Goh, Christabelle S. M.

    AU - Wilson, Neil J.

    AU - Smith, Frances J. D.

    AU - Pohler, Elizabeth

    AU - Simpson, Michael A.

    AU - McLean, W. H. Irwin

    AU - Irvine, Alan D.

    AU - Horowitz, Mia

    AU - McGrath, John A.

    AU - Green, Kathleen J.

    AU - Sprecher, Eli

    PY - 2013

    Y1 - 2013

    N2 - 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.

    AB - 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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    U2 - 10.1038/ng.2739

    DO - 10.1038/ng.2739

    M3 - Letter

    C2 - 23974871

    JO - Nature Genetics

    JF - Nature Genetics

    SN - 1061-4036

    ER -