OPEN The New England journal of medicine | 4 Feb 2016
SE Boyden, A Desai, G Cruse, ML Young, HC Bolan, LM Scott, AR Eisch, RD Long, CR Lee, CL Satorius, AJ Pakstis, A Olivera, JC Mullikin, E Chouery, A Mégarbané, M Medlej-Hashim, KK Kidd, DL Kastner, DD Metcalfe and HD Komarow
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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