{"doi":"10.3390/cells11193071","title":"Novel GATA1 Variant Causing a Bleeding Phenotype Associated with Combined Platelet α-/δ-Storage Pool Deficiency and Mild Dyserythropoiesis Modified by a SLC4A1 Variant","abstract":"<jats:p>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&gt;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&gt;T p.A737V variant maternally transmitted in the daughter may modify the disease to mild spherocytosis and hemolysis.</jats:p>","journal":"Cells","year":2022,"id":607498,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1559895,"name":"Anke Adenaeuer","orcid":"0000-0002-6237-9840","position":1,"is_corresponding":false},{"id":1559897,"name":"Stefanie Sollfrank","orcid":null,"position":2,"is_corresponding":false},{"id":1559900,"name":"Kathrin Groß","orcid":null,"position":3,"is_corresponding":false},{"id":832194,"name":"Friederike Häuser","orcid":"0000-0002-2687-537X","position":4,"is_corresponding":false},{"id":1559903,"name":"Andreas Czwalinna","orcid":null,"position":5,"is_corresponding":false},{"id":1559906,"name":"Josef Erkel","orcid":null,"position":6,"is_corresponding":false},{"id":1559909,"name":"Nele Fritsch","orcid":null,"position":7,"is_corresponding":false},{"id":1559912,"name":"Dana Marandiuc","orcid":null,"position":8,"is_corresponding":false},{"id":791863,"name":"Martin Schaller","orcid":"0000-0002-7930-1919","position":9,"is_corresponding":false},{"id":116269,"name":"Karl J. 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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&gt;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&gt;T p.A737V variant maternally transmitted in the daughter may modify the disease to mild spherocytosis and hemolysis.</jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36231035","pmcid":"PMC9564339","openalex_id":"https://openalex.org/W4297973490","authors":[],"funders":[{"funder_name":"German Federal Ministry of Education and Research","grant_id":"BMBF 01EO1503","title":null}],"total_grants":1,"fwci":1.0917,"citation_percentile":0.78062959,"influential_citations":0,"citation_trend":[{"year":2023,"count":2},{"year":2024,"count":4},{"year":2025,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2073-4409/11/19/3071/pdf?version=1665279734","host_type":"journal"},{"url":"https://www.mdpi.com/2073-4409/11/19/3071/pdf?version=1665279734","host_type":"publisher"},{"url":"https://www.mdpi.com/2073-4409/11/19/3071/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/cells11193071","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36231035","host_type":"repository"},{"url":"https://doaj.org/article/a8cbb3c86a184c079babd3ae268763de","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/cells11193071","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9564339","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9564339","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9564339?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Hemoglobinopathies and Related Disorders","Blood disorders and treatments","Blood groups and transfusion","Anemia","Anion Exchange Protein 1, Erythrocyte","GATA1 Transcription Factor","Hemorrhage","Humans","Male","Phenotype","Platelet Storage Pool Deficiency","Platelet Alpha-Delta Storage Pool Deficiency"],"mesh_terms":["Anemia","Anion Exchange Protein 1, Erythrocyte","Hemorrhage","Humans","Male","Phenotype","Platelet Storage Pool Deficiency","GATA1 Transcription Factor"],"keywords":["Phenotype","Platelet","GATA1","Medicine","Biology","Genetics","Erythropoiesis","Internal medicine","Gene","Anemia","Thrombocytopenia","Whole Exome Sequencing","Storage Pool Deficiency","Inherited Platelet Disorders","Slc4a1"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"refsnp"},{"name":"omim"},{"name":"refseq"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T06:30:07.200893Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}