PMC9464931_01
De novo heterozygous STAT1(c.854A>G) leading to p.Q285R amino acid change in STAT1 gene of the patient. DNA chromatogram of the patient and his parents (wild-type) was detected by whole-exome sequencing.
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The mutation was the first to occur in our patient, and neither of her parents was influenced ( Figure 1 ). Further bone marrow morphology test and biopsy indicated a decline in bone marrow erythrocytes [erythrocytes 0.4% (reference range 15~25%), granulocytes/erythrocytes=158:1(reference range 2~4:1)], leading to the diagnosis of pure red cell aplasia (PRCA) ( Supplementary Figure S1 ).
Chest computed tomography scan. Multiple bronchiectasis were randomly distributed in the bilateral lobe.
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In addition, due to repeated lung infections, the patient developed bronchiectasis ( Figure 2 ).
Enhanced STAT1 and p-STAT1 expression in the GOF patient. (A) Evaluation of STAT1 and p-STAT1 protein level in the GOF patient and healthy control by immunoblotting, at rest, 15', 30', 120' after IFN-gamma stimulation. (B) Patient and healthy control p-STAT1 level 20min after IFN-gamma stimulation, as measured by flow cytometry.
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IFN-gamma could induce abnormally high STAT1 expression and phosphorylation in the patient's PBMCs ( Figure 3A ). In addition, flow cytometry was used to assess the response of p-STAT1 to IFN-gamma stimulation in whole blood, and p-STAT1 levels were higher in STAT1 GOF patients ( Figure 3B ).
Timeline of clinical events and treatment strategies. HSCT, hematopoietic stem cell Transplant.
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