2. Academic Validation
  3. Vibratory Urticaria Associated with a Missense Variant in ADGRE2

Vibratory Urticaria Associated with a Missense Variant in ADGRE2

  • N Engl J Med. 2016 Feb 18;374(7):656-63. doi: 10.1056/NEJMoa1500611.
Steven E Boyden 1,  Avanti Desai,  Glenn Cruse,  Michael L Young,  Hyejeong C Bolan,  Linda M Scott,  A Robin Eisch,  R Daniel Long,  Chyi-Chia R Lee,  Colleen L Satorius,  Andrew J Pakstis,  Ana Olivera,  James C Mullikin,  Eliane Chouery,  André Mégarbané,  Myrna Medlej-Hashim,  Kenneth K Kidd,  Daniel L Kastner,  Dean D Metcalfe,  Hirsh D Komarow
Affiliations

Affiliation

  • 1 From the Inflammatory Disease Section, National Human Genome Research Institute (S.E.B., C.L.S., D.L.K.), Mast Cell Biology Section, National Institute of Allergy and Infectious Diseases, (A.D., G.C., H.C.B., L.M.S., A.R.E., A.O., D.D.M., H.D.K.), Laboratory of Pathology, National Cancer Institute (C.-C.R.L.), and National Institutes of Health (NIH) Intramural Sequencing Center, National Human Genome Research Institute (J.C.M.), NIH, Bethesda, and Clinical Research Directorate-Clinical Monitoring Research Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick (M.L.Y.) - both in Maryland; Veterinary Pathology Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT (R.D.L.); the Department of Genetics, Yale University School of Medicine, New Haven, CT (A.J.P., K.K.K.); Medical Genetics Unit, Saint Joseph University, Beirut (E.C.) and Department of Life and Earth Sciences, Faculty of Sciences II, Lebanese University, Fanar (M.M.-H.) - both in Lebanon; and Institut Jérôme Lejeune, Paris (A.M.).
PMID: 26841242 DOI: 10.1056/NEJMoa1500611
Abstract

Patients with autosomal dominant vibratory urticaria have localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum. We identified a previously unknown missense substitution in ADGRE2 (also known as EMR2), which was predicted to result in the replacement of cysteine with tyrosine at amino acid position 492 (p.C492Y), as the only nonsynonymous variant cosegregating with vibratory urticaria in two large kindreds. The ADGRE2 receptor undergoes autocatalytic cleavage, producing an extracellular subunit that noncovalently binds a transmembrane subunit. We showed that the variant probably destabilizes an autoinhibitory subunit interaction, sensitizing mast cells to IgE-independent vibration-induced degranulation. (Funded by the National Institutes of Health.).

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