NLRP3

Genetic findings for NLRP3 in Schnitzler Syndrome

Variants (2)

VariantTypeFrequencySignificance
Somatic mosaicism (various)somaticRare (2 confirmed cases)Found in patients with the most severe phenotypes. Demonstrates that NLRP3 can be directly causative in some cases.
V198Mgermline1 family studiedFound in 1 patient but 4 asymptomatic carriers across 3 generations — insufficient alone to cause disease.

Clinical implications

Somatic mosaicism (various)

Supports inflammasome-driven model. Does not currently change treatment approach.

Also found in: CAPS (Nearly all cases (germline))

V198M

Low-penetrance variant. Not diagnostic on its own.

Also found in: CAPS (mild forms) (Occasional)

Related molecules

NLRP3strong

Inflammasome sensorDysregulated

Related hypotheses

NLRP3 somatic mosaicism is the primary driver in a subset of patients

20
emerging·8 studies

Pyrin-inflammasome dysfunction (MEFV variants) contributes to pathogenesis

15
emerging·4 studies

Sources (2)

C1de Koning HD et al. (2015) NLRP3 somatic mosaicism in variant Schnitzler · J Allergy Clin ImmunolDOI
C2Rowczenio DM et al. (2018) 32-gene sequencing study · BloodDOI