Vibratory Urticaria Associated with a Missense Variant in ADGRE2

• Published in: The New England journal of medicine Vol. 374; no. 7; pp. 656 - 663
• Main Authors: Boyden, Steven E, Desai, Avanti, Cruse, Glenn, Young, Michael L, Bolan, Hyejeong C, Scott, Linda M, Eisch, A. Robin, Long, R. Daniel, Lee, Chyi-Chia R, Satorius, Colleen L, Pakstis, Andrew J, Olivera, Ana, Mullikin, James C, Chouery, Eliane, Mégarbané, André, Medlej-Hashim, Myrna, Kidd, Kenneth K, Kastner, Daniel L, Metcalfe, Dean D, Komarow, Hirsh D
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 18.02.2016
• Series: Brief Report
• Subjects: Amino acids; Biopsy; Cell Degranulation - genetics; Degranulation; Dermatitis; Dermatology; Female; Histamine; Histamine - blood; Humans; Lebanon; Male; Mast cells; Mast Cells - physiology; Middle Aged; Mutation; Mutation, Missense; Pedigree; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Skin; Skin - pathology; Skin diseases; Tyrosine; Urticaria; Urticaria - blood; Urticaria - etiology; Urticaria - genetics; Vibration - adverse effects; Lebanon
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1500611

A variant in ADGRE2, encoding an adhesion G-protein–coupled receptor, is associated with vibratory urticaria. The variant probably causes disease; if so, it is likely to do so by weakening an autoinhibitory mechanism of the receptor. Physical urticarias are disorders in which localized hives develop in response to any of various stimuli. 1 The histamine release that is associated with urticarias has implicated aberrant degranulation of mast cells in their pathogenesis. 2 Isolated or syndromic cold urticaria can be caused by variants in NLRP3, 3 which encodes a component of the inflammasome signaling complex, or in PLCG2, 4 which encodes a regulatory phospholipase. Otherwise, no pathogenic variants underlying physical urticarias have been identified. ADGRE2 encodes a member of the epidermal growth factor (EGF)–seven transmembrane (TM7) subclass of adhesion G-protein–coupled receptors (GPCRs); the ADGRE2 protein has an N-terminal extracellular . . .