# Case Report: A case of autoinflammatory disease with a novel NLRP12 variant—clinical presentation and successful treatment with baricitinib

## TL;DR

A 16-year-old girl with a rare genetic disorder causing inflammation was successfully treated with baricitinib after a novel NLRP12 gene variant was identified.

## Contribution

First clinical case linking the NLRP12 p.Glu619Gln variant to autoinflammatory disease and demonstrating successful treatment with baricitinib.

## Key findings

- The NLRP12 p.Glu619Gln variant is likely pathogenic and associated with autoinflammatory symptoms.
- Baricitinib treatment rapidly reduced inflammation and IL-6 levels in the patient.
- Structural analysis predicted functional impairment caused by the NLRP12 mutation.

## Abstract

NLRP12-associated autoinflammatory disease (NLRP12-AID) is a rare monogenic disorder. The p.Glu619Gln (c.1855G > C) variant in NLRP12 is classified as a variant of uncertain significance (VUS), with no previously reported clinical cases. We describe a 16-year-old Chinese girl with a 9-year history of periodic high fevers (>39 °C), cold-triggered urticarial rashes, and polyarticular arthralgia. Previous misdiagnoses included recurrent infections and juvenile idiopathic arthritis. Laboratory tests showed elevated levels of interleukin-6 (IL-6) and acute-phase reactants. A lymph node biopsy confirmed necrotizing lymphadenitis. Extensive testing ruled out infections, autoimmune diseases, and cancers. Whole-exome sequencing identified a heterozygous NLRP12 p.Glu619Gln variant. Structural analysis with AlphaFold2 predicted that the mutation causes local structural destabilization and impairs function. After treatment with baricitinib (2 mg/day), the patient experienced rapid symptom relief within 2 weeks, with IL-6 levels decreasing from 17.8 pg./mL to 2.1 pg./mL and maintained clinical control over 12 months of follow-up. This is the first reported case providing multiple lines of evidence linking the NLRP12 p.Glu619Gln VUS to a typical autoinflammatory profile. Characteristic symptoms, inflammatory markers, histopathology, and a notable response to JAK inhibition support the diagnosis. Our findings suggest reclassifying this variant as likely pathogenic and propose baricitinib as a targeted therapy for NLRP12-AID.