RNF213-associated urticarial lesions with hypercytokinemia

Area of Science:

• Genetics
• Immunology
• Dermatology

Background:

• Urticarial lesions can indicate systemic or cutaneous disorders.
• Familial urticarial syndromes are rare and associated with systemic autoinflammatory diseases.

Purpose of the Study:

• Investigate a large family with dominantly inherited chronic urticarial lesions.
• Characterize the genetic and molecular basis of this rare condition.

Main Methods:

• Genetic linkage analysis and whole-exome sequencing were performed on affected family members.
• Cytokine profiling, transcriptomic, and proteomic analyses were conducted.
• In vitro expression of normal and mutated RNF213 (mysterin) was studied.

Main Results:

• A loss-of-function mutation in RNF213 was identified in affected individuals.
• Patients exhibited chronic urticarial flares with high pro- and anti-inflammatory cytokine levels.
• RNF213 interacts with CYLD, a key inflammation regulator, and its mutation affects this interaction.

Conclusions:

• A novel disease entity of chronic urticaria linked to RNF213 loss-of-function is identified.
• This study highlights mysterin's crucial role in innate immunity regulation.
• The findings provide insights into the molecular network of autoinflammatory syndromes.