Novel CARMIL2 (RLTPR) Mutation Presenting with Hyper-IgE and Eosinophilia: A Case Report

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Inborn errors of immunity encompass diverse genetic disorders affecting immune function.
• CARMIL2 (previously RLTPR) deficiency is a rare immune dysregulation disorder linked to allergies, infections, and inflammatory bowel disease.
• It is associated with susceptibility to lymphoproliferative conditions.

Observation:

• A 29-year-old male presented with severe allergies, recurrent skin infections, eosinophilia, and elevated IgE.
• Genetic analysis revealed a homozygous CARMIL2 nonsense mutation in a consanguineous family.
• CARMIL2 is crucial for actin polymerization and cell protrusion formation.

Findings:

• CARMIL2 deficiency impairs T cell activation and maturation via cytoskeletal regulation.
• The mutation disrupts the balance of Th1, Th2, and Th17 immune responses.
• This underscores the gene's critical role in immune homeostasis.

Implications:

• Understanding CARMIL2 mutations enhances diagnosis of similar immune dysregulation phenotypes.
• This research clarifies CARMIL2's impact on immune pathways and T cell development.
• Further studies can guide targeted therapies for CARMIL2-related disorders.