Nokea
You are consulting on a 10-year-old male with severe persistent neutropenia, a history of recurrent infections, and warts. The rest of the peripheral blood count is normal. His mother also has neutropenia. Bone marrow examination shows a hypercellular marrow and retained myeloid cells with vacuolated cytoplasm. There are no abnormalities in the red cells or platelet precursors. Cytogenetics are 46XY. You start granulocyte colony stimulating factor therapy and the neutrophil count increases. A mutation in which of the following genes is most likely to have caused this familial inherited bone marrow failure syndrome?
Correct Answer: A
Rationale: The correct answer is A: CXCR4. In this case, the familial inherited bone marrow failure syndrome with severe neutropenia, recurrent infections, and warts suggests WHIM syndrome. WHIM syndrome is caused by a gain-of-function mutation in the CXCR4 gene, leading to impaired neutrophil trafficking. The symptoms and bone marrow findings in this patient align with WHIM syndrome. Choice B (ELANE) is associated with cyclic neutropenia, not WHIM syndrome. Choice C (GATA 2) is linked to familial myelodysplastic syndromes and acute myeloid leukemia, not WHIM syndrome. Choice D (Mitochondrial DNA) is not associated with WHIM syndrome. Therefore, the mutation in CXCR4 is the most likely cause of the familial inherited bone marrow failure syndrome in this patient.