Introduction: Coronin 1A belongs to a large family of actin regulatory proteins with a role in T cell homeostasis. A role for coronin 1A was also observed in macrophages, NK, and neuronal cells. To date, coronin 1A deficiency has been described in relatively few patients with combined immunodeficiency. Aim: We studied here the molecular and genetic basis of immunodeficiency detected by newborn screening for severe combined immunodeficiency. Methods: Patient data was collected in accordance with REB approved protocols. Immune work up, including T and B cell proliferative responses and serum concentrations of immunoglobulins, was performed. Next generation sequencing techniques and cellular analyses were also utilized. Results: The patient presented with T cell lymphopenia, reduction in CD4+CD45Ra+ cells and hypogammaglobulinemia. Uniquely, she also had persistent severe neutropenia. Whole exome sequencing and Sanger confirmation revealed a novel homozygous mutation in coronin 1A. Conclusion: Coronin 1A deficiency can be detected after birth by T cell receptor excision circle-based newborn screening. Statement of novelty: We report here a patient with a novel mutation in coronin 1A, identified during newborn screening with low T cell receptor excision circle levels and neutropenia, which is a unique finding in this condition.
Newborn screening for severe combined immunodeficiency: Evaluation of a commercial T-cell receptor excision circle-based method in Victorian dried blood spots
