Case Report: Familial Cold Autoinflammatory Syndrome With Double Variant in NLRP12 and SETD1A

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• The inflammasome mediates inflammatory responses via cytokines and pyroptosis.
• NLRP12, a NOD-like receptor, regulates inflammation and inflammasome signaling.
• Mutations in NLRP12 cause familial cold autoinflammatory syndrome type 2 (FCAS2), an autosomal dominant disorder.

Purpose of the Study:

• To investigate the genetic basis of recurrent infections, allergies, and seizures in a pediatric patient.
• To evaluate the potential pathogenic role of identified genetic variants in the patient's clinical presentation.

Main Methods:

• Whole exome sequencing was performed on the pediatric patient.
• Clinical presentation and genetic variants were analyzed in the context of autoinflammatory diseases.

Main Results:

• Exome sequencing identified variants in SETD1A (neurodevelopmental disorders) and NLRP12.
• The NLRP12 variant, previously considered benign, was found in a patient with symptoms suggestive of FCAS2 and immunodeficiency.

Conclusions:

• The NLRP12 variant may possess an underestimated pathogenic role in autoinflammatory diseases.
• This case underscores the need for further research into the clinical variability of autoinflammatory conditions and their genetic underpinnings.
• Developing targeted treatments for autoinflammatory diseases remains crucial.