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Endocrine, Metabolic & Immune Disorders - Drug Targets

Author(s): Raha Zamani*, Samaneh Zoghi*, Sepideh Shahkarami, Simin Seyedpour, Raúl Jimenez Heredia, Kaan Boztug and Nima Rezaei*

DOI: 10.2174/0118715303263327230922043929

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

Page: [596 - 605] Pages: 10

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Abstract

Background: Inborn errors of immunity are a growing group of disorders with a wide spectrum of genotypic and phenotypic profiles. CARMIL2 (previously named RLTPR) deficiency is a recently described cause of immune dysregulation, mainly presenting with allergy, mucocutaneous infections, and inflammatory bowel disease. CARMIL2 deficiency is categorized under diseases of immune dysregulation with susceptibility to lymphoproliferative conditions.

Case Presentation: Here we describe a 29-years-old male from a consanguineous family, with food and sting allergy, allergic rhinitis, facial molluscum contagiosum (viral infection of the skin in the form of umbilicated papules), eosinophilia and highly elevated serum IgE level. Whole exome sequencing revealed numerous homozygous variants, including a CARMIL2 nonsense mutation, a gene regulating actin polymerization, and promoting cell protrusion formation.

Conclusion: The selective role of CARMIL2 in T cell activation and maturation through cytoskeletal organization is proposed to be the cause of immune dysregulation in individuals with CARMIL2 deficiency. CARMIL2 has an important role in immune pathways regulation, through cell maturation and differentiation, giving rise to a balance between Th1, Th2, and Th17 immune response. This case can improve the understanding of the different impacts of CARMIL2 mutations on immune pathways and further guide the diagnosis of patients with similar phenotypes.

Graphical Abstract

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