A 2-month-old boy with Down syndrome develops lethargy, pallor, and hepatosplenomegaly. Peripheral smear shows circulating blasts, and bone marrow evaluation reveals megakaryoblastic proliferation. The mutation that underlies this neonatal hematologic complication of trisomy 21 occurs in which gene?
- A GATA1 ✓
- B JAK2
- C PAX5
- D RUNX1
Explanation
Transient abnormal myelopoiesis (transient myeloproliferative disorder) affects roughly 10% of neonates with Down syndrome and is driven by somatic mutations in GATA1 within fetal megakaryocyte-erythroid precursors. It usually resolves spontaneously but about 20% to 30% of affected infants develop acute megakaryocytic leukemia (AML-M7) by age 5. JAK2 mutations characterize polycythemia vera and related myeloproliferative neoplasms, RUNX1 mutations cause familial platelet disorder and some AMLs, and PAX5 alterations occur in A-ALL, none of which are specific to this entity.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.