mediumGenetic discovery

Deep sequencing reveals somatic mosaicism in 40% of mutation-negative CAPS children

Cryopyrin-Associated Periodic Syndromes →

Summary

Melo Gomes et al. (2025) found somatic NLRP3 mosaicism via amplicon-based deep sequencing in 4/10 mutation-negative CAPS pediatric patients, with allele frequencies as low as 1.9% (Front Pediatr).

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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ID: cryopyrin-associated-periodic-syndromes-update-1Type: genetic_discoveryImpact: medium