A novel missense mutation in CIAS1 encoding the pyrin-like protein, cryopyrin, causes familial cold autoinflammatory syndrome in a family of Ethiopian origin.
BACKGROUND
Cold-induced urticaria is a form of physical urticaria which is characterized by rapid onset of pruritus, erythema, and swelling after exposure to a cold stimulus. Familial cold autoinflammatory syndrome (FCAS) is a rare autosomal-dominant condition characterized by unremitting attacks of cold-induced urticaria, often accompanied by other systemic manifestations. The disorder was previously shown to be caused by mutations in CIAS1, encoding a pyrin-like protein also involved in the pathogenesis of Muckle-Wells syndrome (MWS), and chronic infantile neurological cutaneous and articular syndrome (CINCA).


METHODS
In the present study, using direct sequencing, we assessed a two-generation family of Jewish Ethiopian origin, including 3 members affected with FCAS.


RESULTS
We identified a novel CIAS1 mutation, F525C. The mutation was shown to affect a highly conserved residue of the protein and to segregate with the disease throughout the extended family.


CONCLUSIONS
Our results add to the expanding spectrum of mutations in CIAS1 and provide evidence for striking phenotypic heterogeneity in inherited autoinflammatory syndromes. This is the first report of inherited cold urticaria in a family of Ethiopian origin.
Shalev
Stavit A
SA
The Genetic Institute, Ha'Emek Medical Center, Afula, Israel.
Sprecher
Eli
E
Indelman
Margarita
M
Hujirat
Yaser
Y
Bergman
Reuven
R
Rottem
Menachem
M
D000328:Adult; D001327:Autoimmune Diseases / Q000235:genetics* / Q000503:physiopathology; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D003080:Cold Temperature / Q000009:adverse effects*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D020125:Mutation, Missense; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013577:Syndrome; D014581:Urticaria / Q000235:genetics* / Q000503:physiopathology
D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human