Association Between Pathogenic Variants in NLRP12 and Autoinflammatory Disease: A Comprehensive Systematic Review.

Area of Science:

• Genetics
• Immunology
• Rheumatology

Background:

• Systemic auto-inflammatory diseases (SAID) are rare inherited immune disorders.
• Pathogenic variants in the NLRP12 gene are implicated in autoinflammatory syndromes.
• NLRP12-associated autoinflammatory disease (NLRP12-AID) requires accurate diagnosis.

Purpose of the Study:

• Identify causal variants in the NLRP12 gene.
• Discuss the pathogenesis, clinical features, and treatments of NLRP12-AID.
• Evaluate the role of NLRP12 variants in differential diagnosis.

Main Methods:

• Systematic literature review using EMBASE, Scopus, ScienceDirect, Web of Science, and PubMed.
• Analysis of 874 articles, with 27 meeting inclusion criteria.
• Identification and classification of NLRP12 gene variants.

Main Results:

• 103 patients with NLRP12 variants reported; 60 variants identified (49 VUS, pathogenic, or likely pathogenic).
• Mean age of onset: 13.18 years; fever (90%), rash/urticaria (59%), myalgia/arthralgia (39%), abdominal pain/diarrhea (50%).
• Diverse clinical features affecting musculoskeletal and gastrointestinal systems, overlapping with Familial Cold Autoinflammatory Syndrome (FCAS).

Conclusions:

• NLRP12-AID presents with varied symptoms and can be misdiagnosed due to variable expression and incomplete penetrance.
• Genetic evaluation of NLRP12 is recommended for patients with undifferentiated recurrent fever.
• Understanding NLRP12 variants aids in differential diagnosis and management of autoinflammatory diseases.