Gene

MYD88

1 variant(s) documented across Schnitzler Syndrome

Variants

VariantTypeFrequency in diseaseSignificanceAlso found in
L265P (somatic)somatic~30% of tested patientsThe most significant genetic finding. Same mutation found in >90% of Waldenström's macroglobulinemia. Drives persistent NF-κB activation.Waldenström's macroglobulinemia (>90%)

Clinical implications

L265P (somatic)

Supports shared pathogenic mechanism with WM. May predict response to ibrutinib.

Testing: allele-specific PCR, Sanger sequencing

Related molecules in pathway

MYD88moderate

TLR signalling adaptor — L265P in ~30%

Related hypotheses

Shared MYD88/NF-κB mechanism drives both autoinflammation and B-cell clonality

55
leading·48 studies

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)

C4Pathak S et al. (2019) MYD88 L265P in 30% of Schnitzler patientsPubMed ↗
B7Van Leersum FS et al. (2019) Shared MYD88/NF-κB mechanism hypothesisDOI ↗