D1.413 - A Novel Variant of CORO1A Gene Contributing to The Development of Primary Immunodeficiency in Children

Introduction: The case report describes a novel finding of a homozygous variant in the CORO1A gene, associated with severe combined immunodeficiency (SCID), in a 9-year-old female patient with recurrent infections and unique immunological features, including T-cell lymphocytosis and B-cell lymphopenia.

Case History and Examination: A 9-year-old female with a known history of recurrent pneumonia presented to the emergency department with a 2-week history of intermittent fever, progressive lethargy, and pallor. Her past medical history was remarkable for multiple hospital admissions secondary to community-acquired pneumonia and urinary tract infections, totaling four admissions to date. Family history was significant for consanguinity between parents and a healthy 4-year-old younger male sibling. Chest computed tomography (CT) demonstrated bilateral diffuse centrilobular nodules, scattered ground-glass opacities, and left lower lobe consolidation, in addition to a tree-in-bud pattern. Immunological evaluation revealed T-cell lymphocytosis, B-cell lymphopenia, and a decreased CD4/CD8 ratio. Based on these findings, the pediatric allergy and immunology team recommended genetic testing for primary immunodeficiency. The panel identified a homozygous variant of uncertain significance (VUS) in the CORO1A gene.

Discussion: 

 ^{The majority of SCID disorders emerge as a result of profound defect in T-cell proliferation and maturation in the thymus leading to T-lymphopenia.Both typical and atypical SCID require persistent T-cell lymphopenia confirmed on repeated testing. To our knowledge, this is the first novel report of primary immunodeficiency manifesting by T-Cell lymphocytosis, B-Cell lymphopenia with low CD4/CD8 ratio implicating the CORO1A gene. Although Coronin-1A–deficient patients possess a thymus, Punwani, et al. proposed that impaired central T-cell development—due to defective thymic maturation and a propensity for apoptosis—may explain the observed T-cell lymphopenia. However, peripheral immune defects, including unresponsiveness to T-cell receptor (TCR) ligation or impaired migration to sites of infection, have also been hypothesized. In our case, the presence of T-cell lymphocytosis supports the latter mechanism, suggesting that defective T-cell migration or signaling, rather than thymic egress failure, may underlie the immunological phenotype.}

Conclusion: The novel homozygous variant in the CORO1A gene suggests the likelihood of an atypical form of severe combined immunodeficiency (SCID).  These findings indicate possible involvement of T-cell receptor signaling or lymphocyte migration defects in the pathophysiology, leading to impaired immune function associated with Coronin protein deficiency.