## Why FLI1 is right The terminal 11q23 deletion marked **A** (del(11)(q23→qter)) in Jacobsen syndrome disrupts the FLI1 gene, a critical megakaryocyte transcription factor. FLI1 haploinsufficiency causes Paris-Trousseau syndrome — congenital thrombocytopenia with pathognomonic giant alpha-granules in platelets — which occurs in ~88% of Jacobsen patients. The giant granules are visible on electron microscopy and reflect abnormal megakaryocyte maturation due to FLI1 loss. This is the most distinctive hematologic feature of the syndrome and directly links the deleted region to the patient's bleeding diathesis (Robbins 10e Ch 5; Nelson Pediatrics 21e Ch 98). ## Why each distractor is wrong - **JAM3 (vascular development)**: While JAM3 is deleted in the 11q23 region and contributes to vascular anomalies, it does not account for the characteristic giant platelet alpha-granules. JAM3 disruption affects endothelial development, not megakaryocyte granule morphology. - **ETS1 (cardiac/immune transcription factor)**: ETS1 deletion contributes to congenital heart disease and immune deficiency in Jacobsen syndrome, but it does not explain the pathognomonic giant alpha-granules. The platelet morphology is FLI1-specific. - **BARX2 (developmental homeobox gene)**: BARX2 is involved in craniofacial and skeletal development, accounting for trigonocephaly and skeletal anomalies, but has no role in megakaryocyte differentiation or platelet granule formation. **High-Yield:** Jacobsen syndrome = trigonocephaly + thrombocytopenia with giant platelet alpha-granules + CHD; FLI1 haploinsufficiency = Paris-Trousseau syndrome (pathognomonic). [cite:Robbins 10e Ch 5; Nelson Pediatrics 21e Ch 98]
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