Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation - PubMed (original) (raw)
. 2001 Jul 1;98(1):85-92.
doi: 10.1182/blood.v98.1.85.
Affiliations
- PMID: 11418466
- DOI: 10.1182/blood.v98.1.85
Free article
Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation
K Freson et al. Blood. 2001.
Free article
Abstract
A new mutation is described in the X-linked gene GATA1, resulting in macrothrombocytopenia and mild dyserythropoietic features but no marked anemia in a 4-generation family. The molecular basis for the observed phenotype is a substitution of glycine for aspartate in the strictly conserved codon 218 (D218G) of the amino-terminal zinc finger loop of the transcription factor GATA1. Zinc finger interaction studies demonstrated that this mutation results in a weak loss of affinity of GATA1 for its essential cofactor FOG1, whereas direct D218G-GATA1 binding to DNA was normal. The phenotypic effects of this mutation in the patients' platelets have been studied. Semiquantitative RNA analysis, normalized for beta-actin messenger RNA, showed extremely low transcription of the GATA1 target genes GPIbbeta and GPIX but also a significantly lower expression of the nondirectly GATA1-regulated Gsalpha gene, suggestive of incomplete megakaryocyte maturation. In contrast, GPIIIa expression was close to normal in agreement with its early appearance during megakaryocyte differentiation. Flow cytometric analysis of patient platelets confirmed the existence of a platelet population with abnormal size distribution and reduced GPIb complex levels but with normal GPIIIa expression. It also showed the presence of very immature platelets lacking almost all membrane glycoproteins studied (GPIbalpha, GPIbbeta, GPIIIa, GPIX, and GPV). Patients' platelets showed weak ristocetin-induced agglutination, compatible with the disturbed GPIb complex. Accordingly, electron microscopy of the patients' platelets revealed giant platelets with cytoplasmic clusters consisting of smooth endoplasmic reticulum and abnormal membrane complexes. In conclusion, GATA1 mutations can lead to isolated X-linked macrothrombocytopenia without anemia.
Similar articles
- GATA1 in Normal and Pathologic Megakaryopoiesis and Platelet Development.
Takasaki K, Chou ST. Takasaki K, et al. Adv Exp Med Biol. 2024;1459:261-287. doi: 10.1007/978-3-031-62731-6_12. Adv Exp Med Biol. 2024. PMID: 39017848 Review. - Molecular cloning and characterization of the GATA1 cofactor human FOG1 and assessment of its binding to GATA1 proteins carrying D218 substitutions.
Freson K, Thys C, Wittewrongel C, Vermylen J, Hoylaerts MF, Van Geet C. Freson K, et al. Hum Genet. 2003 Jan;112(1):42-9. doi: 10.1007/s00439-002-0832-1. Epub 2002 Oct 16. Hum Genet. 2003. PMID: 12483298 - X-linked thrombocytopenia caused by a novel mutation of GATA-1.
Mehaffey MG, Newton AL, Gandhi MJ, Crossley M, Drachman JG. Mehaffey MG, et al. Blood. 2001 Nov 1;98(9):2681-8. doi: 10.1182/blood.v98.9.2681. Blood. 2001. PMID: 11675338 - GATA1 in normal and malignant hematopoiesis.
Crispino JD. Crispino JD. Semin Cell Dev Biol. 2005 Feb;16(1):137-47. doi: 10.1016/j.semcdb.2004.11.002. Epub 2004 Dec 13. Semin Cell Dev Biol. 2005. PMID: 15659348 Review.
Cited by
- GATA1 in Normal and Pathologic Megakaryopoiesis and Platelet Development.
Takasaki K, Chou ST. Takasaki K, et al. Adv Exp Med Biol. 2024;1459:261-287. doi: 10.1007/978-3-031-62731-6_12. Adv Exp Med Biol. 2024. PMID: 39017848 Review. - Scoping Review on Platelets and Tumor Angiogenesis: Do We Need More Evidence or Better Analysis?
Filippelli A, Del Gaudio C, Simonis V, Ciccone V, Spini A, Donnini S. Filippelli A, et al. Int J Mol Sci. 2022 Nov 2;23(21):13401. doi: 10.3390/ijms232113401. Int J Mol Sci. 2022. PMID: 36362186 Free PMC article. Review. - Gata1s mutant mice display persistent defects in the erythroid lineage.
Ling T, Zhang K, Yang J, Gurbuxani S, Crispino JD. Ling T, et al. Blood Adv. 2023 Jul 11;7(13):3253-3264. doi: 10.1182/bloodadvances.2022008124. Blood Adv. 2023. PMID: 36350717 Free PMC article. - A Novel GATA1 Variant in the C-Terminal Zinc Finger Compared with the Platelet Phenotype of Patients with A Likely Pathogenic Variant in the N-Terminal Zinc Finger.
Bastida JM, Malvestiti S, Boeckelmann D, Palma-Barqueros V, Wolter M, Lozano ML, Glonnegger H, Benito R, Zaninetti C, Sobotta F, Schilling FH, Morgan NV, Freson K, Rivera J, Zieger B. Bastida JM, et al. Cells. 2022 Oct 14;11(20):3223. doi: 10.3390/cells11203223. Cells. 2022. PMID: 36291092 Free PMC article. - Novel GATA1 Variant Causing a Bleeding Phenotype Associated with Combined Platelet α-/δ-Storage Pool Deficiency and Mild Dyserythropoiesis Modified by a SLC4A1 Variant.
Jurk K, Adenaeuer A, Sollfrank S, Groß K, Häuser F, Czwalinna A, Erkel J, Fritsch N, Marandiuc D, Schaller M, Lackner KJ, Rossmann H, Bergmann F. Jurk K, et al. Cells. 2022 Sep 29;11(19):3071. doi: 10.3390/cells11193071. Cells. 2022. PMID: 36231035 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases