mediumDiagnostic advance

Cryo-sensitive aggregation mechanism explains cold-triggered FCAS

Cryopyrin-Associated Periodic Syndromes →

Summary

Karasawa et al. (2022) showed CAPS-associated NLRP3 mutants form cryo-sensitive aggregates that scaffold inflammasome activation, providing mechanistic explanation for cold-triggered FCAS episodes (eLife).

Related genes

NLRP3Multiple pathogenic variants (>250)
Gain-of-function mutations causing constitutive inflammasome activation. Most in exon 3 (NACHT domain).
NLRP3R260W
Most frequent MWS-associated variant in French population.
NLRP3T348M
Associated with early onset, chronic course, hearing loss.
NLRP3Somatic mosaicism variants
Low-level allele frequency (1.9–45%); can increase over time. Explains 'mutation-negative' CAPS.
NLRP3De novo mutations
Spontaneous new mutations; no family history.
NLRP3Y861 LRR domain variants
Atypical phenotype with minimal cold-triggered rash.

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highMechanism

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ID: cryopyrin-associated-periodic-syndromes-update-2Type: diagnostic_advanceImpact: medium