Abstract |
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.
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Authors | Kerstin Jurk, Anke Adenaeuer, Stefanie Sollfrank, Kathrin Groß, Friederike Häuser, Andreas Czwalinna, Josef Erkel, Nele Fritsch, Dana Marandiuc, Martin Schaller, Karl J Lackner, Heidi Rossmann, Frauke Bergmann |
Journal | Cells
(Cells)
Vol. 11
Issue 19
(09 29 2022)
ISSN: 2073-4409 [Electronic] Switzerland |
PMID | 36231035
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anion Exchange Protein 1, Erythrocyte
- GATA1 Transcription Factor
- GATA1 protein, human
- SLC4A1 protein, human
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Topics |
- Anemia
- Anion Exchange Protein 1, Erythrocyte
- GATA1 Transcription Factor
(genetics)
- Hemorrhage
(genetics)
- Humans
- Male
- Phenotype
- Platelet Storage Pool Deficiency
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