Gene Mutation Provides Clue to Vibratory Urticaria

Genetic mutation have been discovered that underlies this rare disorder which manifests as itchy red welts, or hives, and other allergic symptoms such as flushing, headaches, fatigue, blurry vision or a metallic taste in the mouth can then occur. Although these symptoms normally fade within an hour, the reaction may occur several times a day.

Scientists at the US National Institutes of Health (NIH; Bethesda, MD, USA) evaluated three families who have experienced the disorder through several generations. The evaluation included a forearm vortex challenge, serum histamine measurements, and findings on skin biopsies. They performed genetic analysis of the families with vibratory urticaria by means of linkage scans, exome sequencing, and Sanger sequencing.

Serum histamine levels were measured from serial blood draws during the 60 minute post vortex challenge period using a competitive enzyme immunoassay (SPI-Bio; Montigny le Bretonneux, France). Serum tryptase levels from the same time points were measured using the ImmunoCAP 100 system (Phadia; Uppsala, Sweden). Immunohistochemistry was performed using the Discovery XT instrument with RedMap detection kit (Ventana Medical Systems; Tucson, AZ, USA). Polymerase chain reaction (PCR) and Sanger sequencing were performed according to standard protocols. The teams carried out DNA sequencing on 36 affected and unaffected members of the three families.

The scientists found a single mutation in the Adhesion G Protein-Coupled Receptor E2 (ADGRE2) gene that was shared by family members with vibratory urticaria but not present in unaffected people. The ADGRE2 gene provides instructions for production of ADGRE2 protein, present on the surface of several types of immune cells, including mast cells. In ADGRE2, there is a beta subunit inside the cell's outer membrane and an alpha subunit on the outer surface of the cell. Normally, these two subunits interact, staying close together, but in people with vibratory urticaria, the team observed a less stable interaction. When the subunits separate, the investigators believe that the beta subunit produces signals inside mast cells that lead to degranulation. This is what leads to hives and other allergy symptoms. The study was published on February 3, 2016, in the New England Journal of Medicine (NEJM).

Related Links:
US National Institutes of Health
SPI-Bio
Phadia