Title:Novel CARMIL2 (RLTPR) Mutation Presenting with Hyper-IgE and
Eosinophilia: A Case Report
Volume: 24
Issue: 5
Author(s): Raha Zamani*, Samaneh Zoghi*, Sepideh Shahkarami, Simin Seyedpour, Raúl Jimenez Heredia, Kaan Boztug and Nima Rezaei*
Affiliation:
- Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria
- St. Anna Children’s Cancer Research Institute (CCRI), Vienna, Austria
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
- Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
Keywords:
Inborn errors of immunity, CARMIL2-deficiency, molluscum contagiosum, Hyper-IgE syndromes, diseases of immune dysregulation, whole-exome sequencing.
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.