A Novel Variant of CORO1A Gene Contributing to the Development of Primary Immunodeficiency in Children

Abstract

Introduction: The case report describes a novel finding of a homozygous variant in the coronin 1A (CORO1A) gene, associated with atypical severe combined immunodeficiency (SCID) in a 9-year-old female patient with recurrent infections and unique immunological features, including periodic T-cell lymphocytosis and T- 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. Pathogenic variants in CORO1A are associated with autosomal recessive CORO1A-related SCID.

Conclusion: The novel homozygous variant in the CORO1A gene suggests the likelihood of an atypical form of SCID, characterized by periodic T-cell lymphocytosis, T-cell lymphopenia, B-cell lymphopenia, and a low CD4/CD8 ratio, expanding the spectrum of CORO1A deficiency.

Keywords: B-cell and CORO1A; T-cell; severe combined immunodeficiency.