Case Report: Novel CXCR2 compound heterozygous variants in an infant with neutropenia

Congenital neutropenia refers to a group of rare inherited disorders in which neutrophil development or release is disrupted, predisposing affected children to frequent infections. Among the genes involved, CXCR2 loss-of-function variants have recently been recognized as a distinct cause of the disease. Here, we report a 12-month-old Chinese boy, who presented with repeated febrile respiratory illnesses and intermittent neutropenia since the age of 10 months. During each episode of the child's viral infection, absolute neutrophil counts ranged between 0.13 and 0.44 ×10⁹/L, while hemoglobin and platelet values remained within the expected range. Lymphocyte subsets and immunoglobulin levels were normal. Whole-exome sequencing revealed two novel CXCR2 variants: a frameshift mutation (c.665delT, p.Val222GlyfsTer4) from his mother and a missense mutation (c.748A>C, p.Met250Leu) from his father. He required intermittent courses of granulocyte colony-stimulating factor and broad-spectrum antibiotics during neutropenic fever episodes. This case expands the mutational and phenotypic spectrum of CXCR2-related congenital neutropenia and highlights the value of genetic testing for infants with unexplained chronic neutropenia and recurrent infections.