biostudies-literatureBoyden SECCR NIH HHSIntramural NIH HHSNCI NIH HHS656-63https://www.ebi.ac.uk/biostudies/studies/S-EPMC4782791biostudies-literatureUnknown374(7)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-indThe New England journal of medicineVibratory Urticaria Associated with a Missense Variant in ADGRE2.PMC4782791HHSN261200800001EHHSN261200800001CZIA AI001091Olivera AKastner DLEisch ARMetcalfe DDChouery EMedlej-Hashim MYoung MLKidd KKBoyden SEScott LMCruse GKomarow HDLong RDDesai ABolan HCLee CCSatorius CLMullikin JCPakstis AJMegarbane AfalseVibratory Urticaria Associated with a Missense Variant in ADGRE2.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-ind2016-01-01T00:00:00Z2016 Feb2026-05-04T13:46:51.841Z2019-03-27T02:10:40ZS-EPMC47827912684124210.1056/NEJMoa150061110.1056/nejmoa1500611