Combined Immunodeficiency Associated with Two Novel CARMIL2 Mutations: A Case Series

Area of Science:

• Immunology
• Genetics
• Infectious Diseases

Background:

• Combined immunodeficiency (CID) due to CARMIL2 mutations is a rare autosomal recessive primary immunodeficiency.
• It is characterized by impaired T-cell activation and function, leading to diverse clinical manifestations.
• Fewer than 50 cases have been reported globally.

Purpose of the Study:

• To describe the clinical and genetic features of five Palestinian patients with homozygous CARMIL2 mutations.
• To report the first case of recurrent visceral leishmaniasis associated with CARMIL2 deficiency.
• To highlight the clinical heterogeneity and expand the phenotypic spectrum of CARMIL2-associated immunodeficiency.

Main Methods:

• Retrospective case series.
• Whole-exome sequencing for genetic diagnosis.
• Clinical and immunological assessment of patients.

Main Results:

• Five patients with homozygous CARMIL2 mutations were identified, exhibiting symptoms like chronic dermatitis, recurrent infections, and cytomegalovirus disease.
• Two novel homozygous variants (c.1865C>T and c.1973C>T) were discovered.
• One patient presented with recurrent visceral leishmaniasis, an unprecedented association with CARMIL2 deficiency.

Conclusions:

• CARMIL2-associated immunodeficiency presents with significant clinical heterogeneity.
• Genetic testing is crucial for diagnosing atypical or recurrent infections, especially in populations with high consanguinity.
• The association with visceral leishmaniasis broadens the understanding of CARMIL2 deficiency's clinical spectrum.