دورية أكاديمية
Novel GATA1 Variant Causing a Bleeding Phenotype Associated with Combined Platelet α-/δ-Storage Pool Deficiency and Mild Dyserythropoiesis Modified by a SLC4A1 Variant.
| العنوان: | Novel GATA1 Variant Causing a Bleeding Phenotype Associated with Combined Platelet α-/δ-Storage Pool Deficiency and Mild Dyserythropoiesis Modified by a SLC4A1 Variant. |
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| المؤلفون: | Jurk, Kerstin, Adenaeuer, Anke, Sollfrank, Stefanie, Groß, Kathrin, Häuser, Friederike, Czwalinna, Andreas, Erkel, Josef, Fritsch, Nele, Marandiuc, Dana, Schaller, Martin, Lackner, Karl J., Rossmann, Heidi, Bergmann, Frauke |
| المصدر: | Cells (2073-4409); Oct2022, Vol. 11 Issue 19, p3071, 23p |
| مصطلحات موضوعية: | BLOOD platelet aggregation, BLOOD platelets, ZINC-finger proteins, PHENOTYPES, MISSENSE mutation, LIGHT transmission, PLATELET count, BLOOD coagulation factor XIII |
| مستخلص: | Germline defects in the transcription factor GATA1 are known to cause dyserythropoiesis with(out) anemia and variable abnormalities in platelet count and function. However, damaging variants closely located to the C-terminal zinc finger domain of GATA1 are nearly unknown. In this study, a 36-year-old male index patient and his 4-year-old daughter suffered from moderate mucocutaneous bleeding diathesis since birth. Whole exome sequencing detected a novel hemizygous GATA1 missense variant, c.886A>C p.T296P, located between the C-terminal zinc finger and the nuclear localization sequence with non-random X-chromosome inactivation in the heterozygous daughter. Blood smears from both patients demonstrated large platelet fractions and moderate thrombocytopenia in the index. Flow cytometry and electron microscopy analysis supported a combined α-/δ (AN-subtype)-storage pool deficiency as cause for impaired agonist-induced platelet aggregation (light transmission aggregometry) and granule exocytosis (flow cytometry). The absence of BCAM in the index (Lu(a-b-)) and its low expression in the daughter (Lu(a-b+)) confirmed a less obvious effect of defective GATA1 also on erythrocytes. Borderline anemia, elevated HbF levels, and differential transcription of GATA1-regulated genes indicated mild dyserythropoiesis in both patients. Furthermore, a mild SLC4A1 defect associated with a heterozygous SLC4A1 c.2210C>T p.A737V variant maternally transmitted in the daughter may modify the disease to mild spherocytosis and hemolysis. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: | Complementary Index |
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