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. Simpson; W. H. Irwin McLean; Alan D. Irvine; Mia Horowitz; John A. McGrath; Kathleen J. Green; Eli Sprecher

doi:10.1038/ng.2739

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 journal › Letter › peer-review

271 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 language	English
Journal	Nature Genetics
Early online date	25 Aug 2013
DOIs	https://doi.org/10.1038/ng.2739
Publication status	Published - 2013

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10.1038/ng.2739

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Samuelov, L., Sarig, O., Harmon, R. M., Rapaport, D., Ishida-Yamamoto, A., Isakov, O., Koetsier, J. L., Gat, A., Goldberg, I., Bergman, R., Spiegel, R., Eytan, O., Geller, S., Peleg, S., Shomron, N., Goh, C. S. M., Wilson, N. J., Smith, F. J. D., Pohler, E., ... Sprecher, E. (2013). Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nature Genetics. https://doi.org/10.1038/ng.2739

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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

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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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DO - 10.1038/ng.2739

M3 - Letter

C2 - 23974871

SN - 1061-4036

JO - Nature Genetics

JF - Nature Genetics

ER -

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

Abstract

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Dermatology and Genetic Medicine (Strategic Grant) (Joint with Kings College London)

Human and Mouse Genetics Studies of Filaggrin-Related Proteins in Eczema and Allergy (Joint with Trinity College Dublin)

Aref#d: 22163. The Establishment of a Large Case Collection of Childhood Atopic Dermatitis: A Resource for Gemetoc Research (Joint with Trinity College Dublin)

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

Abstract

Access to Document

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Projects

Dermatology and Genetic Medicine (Strategic Grant) (Joint with Kings College London)

Human and Mouse Genetics Studies of Filaggrin-Related Proteins in Eczema and Allergy (Joint with Trinity College Dublin)

Aref#d: 22163. The Establishment of a Large Case Collection of Childhood Atopic Dermatitis: A Resource for Gemetoc Research (Joint with Trinity College Dublin)

Cite this