Abstract Number: LPB0080
Meeting: ISTH 2021 Congress
Background: Few known germline variants in the X-linked transcription factor GATA-1 give rise to heterogeneous thrombocytopenia, dyserythropoietic anemia and platelet dysfunction. The c.1240T>C [p.X414R] variant resulting in 42 amino acid extralarge GATA-1, was found in a single family with mild macrothrombocytopenia and the rare X-linked blood group Lutheran (Lu) a- b- (Lu null) standing for lack of Lu antigen on erythrocytes.
Aims: To explore and confirm the association of GATA-1 p.X414R variant and the Lu null phenotype.
Methods: Two patients (Index case [IC] and son [S]) with lifelong macrothrombocytopenia and moderate bleeding enrolled the Spanish Project of Inherited Platelet Disorders. Clinical assessment, platelet phenotyping and DNA analysis were undertaken.
Results: The IC parents were first cousins. His mother, who died of sudden death from cardiomyopathy, and other maternal relatives had macrothrombocytopenia. The IC suffered from intraparenchymal hematoma following exertional syncope, required several surgery interventions due to neurological complications and platelet transfusions. A hypertrophic septal cardiomyopathy was discovered. His thrombocytopenic son has lifelong epilepsy and his untreated thrombocytopenia improved over the years. Complete blood cell analysis confirmed severe and moderate macrothrombocytopenia in IC and S (1 and 73×109/l; non-recordable MPV). Large platelets were observed in stained blood smear. Flow cytometric studies showed large platelets and about 50% increased platelet expression of major glycoproteins (Ib/IX, IIb/IIIa Ia and GPVI). Agonist-induced fibrinogen binding and α- and δ-granule secretion were unaffected. High throughput sequencing gene panel and Sanger confirmation, identified IC and S as hemizygous carriers for the rare GATA-1 variant p.X414R. Serological phenotyping of S red blood cells corroborated the Lua-/Lub- phenotype. His non-thrombocytopenic mother, sister and brother, expressed Lua-/Lub+ on red blood cells. IC died before red cell analysis could be performed.
Conclusions: We report the second pedigree with thrombocytopenia associated to the GATA-1 p.X414R variant, consolidating the relationship of this rare variant with Lu null phenotype.
To cite this abstract in AMA style:Rodriguez-Alén A, Palma-Barqueros V, Rollón-Simón N, Revilla N, Bohdan N, Padilla J, Zamora-Cánovas A, Marín-Quílez A, Sánchez-Fuentes A, González-Porras JR, Vicente V, Cuesta J, Lozano ML, Bastida JM, Pozo R. Clinical and Biological Assessment of the Second Pedigree Affected with X-linked GATA-1 Related Thrombocytopenia and Blood Group Lutheran Null [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/clinical-and-biological-assessment-of-the-second-pedigree-affected-with-x-linked-gata-1-related-thrombocytopenia-and-blood-group-lutheran-null/. Accessed November 29, 2023.
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