Advanced search
1 file | 2.02 MB Add to list

Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency

(2020) LEUKEMIA. 34(10). p.2673-2687
Author
Organization
Abstract
Deficiency of the transcription factor GATA2 is a highly penetrant genetic disorder predisposing to myelodysplastic syndromes (MDS) and immunodeficiency. It has been recognized as the most common cause underlying primary MDS in children. Triggered by the discovery of a recurrent synonymousGATA2variant, we systematically investigated 911 patients with phenotype of pediatric MDS or cellular deficiencies for the presence of synonymous alterations inGATA2. In total, we identified nine individuals with five heterozygous synonymous mutations: c.351C>G, p.T117T (N = 4); c.649C>T, p.L217L; c.981G>A, p.G327G; c.1023C>T, p.A341A; and c.1416G>A, p.P472P (N = 2). They accounted for 8.2% (9/110) of cases with GATA2 deficiency in our cohort and resulted in selective loss of mutant RNA. While for the hotspot mutation (c.351C>G) a splicing error leading to RNA and protein reduction was identified, severe, likely late stage RNA loss without splicing disruption was found for other mutations. Finally, the synonymous mutations did not alter protein function or stability. In summary, synonymousGATA2substitutions are a new common cause of GATA2 deficiency. These findings have broad implications for genetic counseling and pathogenic variant discovery in Mendelian disorders.
Keywords
WORLD-HEALTH-ORGANIZATION, MYELOID NEOPLASMS, LEUKEMIA, DIFFERENTIATION, CLASSIFICATION, TRANSCRIPTION, EXPRESSION, REVISION, ABSENCE, VARIANT

Downloads

  • Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 2.02 MB

Citation

Please use this url to cite or link to this publication:

MLA
Kozyra, Emilia J., et al. “Synonymous GATA2 Mutations Result in Selective Loss of Mutated RNA and Are Common in Patients with GATA2 Deficiency.” LEUKEMIA, vol. 34, no. 10, 2020, pp. 2673–87, doi:10.1038/s41375-020-0899-5.
APA
Kozyra, E. J., Pastor, V. B., Lefkopoulos, S., Sahoo, S. S., Busch, H., Voss, R. K., … Wlodarski, M. W. (2020). Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency. LEUKEMIA, 34(10), 2673–2687. https://doi.org/10.1038/s41375-020-0899-5
Chicago author-date
Kozyra, Emilia J., Victor B. Pastor, Stylianos Lefkopoulos, Sushree S. Sahoo, Hauke Busch, Rebecca K. Voss, Miriam Erlacher, et al. 2020. “Synonymous GATA2 Mutations Result in Selective Loss of Mutated RNA and Are Common in Patients with GATA2 Deficiency.” LEUKEMIA 34 (10): 2673–87. https://doi.org/10.1038/s41375-020-0899-5.
Chicago author-date (all authors)
Kozyra, Emilia J., Victor B. Pastor, Stylianos Lefkopoulos, Sushree S. Sahoo, Hauke Busch, Rebecca K. Voss, Miriam Erlacher, Dirk Lebrecht, Enikoe A. Szvetnik, Shinsuke Hirabayashi, Ramunè Pasauliene, Lucia Pedace, Marco Tartaglia, Christian Klemann, Patrick Metzger, Melanie Boerries, Albert Catala, Henrik Hasle, Valerie de Haas, Krisztian Kallay, Riccardo Masetti, Barbara De Moerloose, Michael Dworzak, Markus Schmugge, Owen Smith, Jan Stary, Ester Mejstrikova, Marek Ussowicz, Emma Morris, Preeti Singh, Matthew Collin, Marta Derecka, Gudrun Göhring, Christian Flotho, Brigitte Strahm, Franco Locatelli, Charlotte M. Niemeyer, Eirini Trompouki, and Marcin W. Wlodarski. 2020. “Synonymous GATA2 Mutations Result in Selective Loss of Mutated RNA and Are Common in Patients with GATA2 Deficiency.” LEUKEMIA 34 (10): 2673–2687. doi:10.1038/s41375-020-0899-5.
Vancouver
1.
Kozyra EJ, Pastor VB, Lefkopoulos S, Sahoo SS, Busch H, Voss RK, et al. Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency. LEUKEMIA. 2020;34(10):2673–87.
IEEE
[1]
E. J. Kozyra et al., “Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency,” LEUKEMIA, vol. 34, no. 10, pp. 2673–2687, 2020.
@article{8672440,
  abstract     = {{Deficiency of the transcription factor GATA2 is a highly penetrant genetic disorder predisposing to myelodysplastic syndromes (MDS) and immunodeficiency. It has been recognized as the most common cause underlying primary MDS in children. Triggered by the discovery of a recurrent synonymousGATA2variant, we systematically investigated 911 patients with phenotype of pediatric MDS or cellular deficiencies for the presence of synonymous alterations inGATA2. In total, we identified nine individuals with five heterozygous synonymous mutations: c.351C>G, p.T117T (N = 4); c.649C>T, p.L217L; c.981G>A, p.G327G; c.1023C>T, p.A341A; and c.1416G>A, p.P472P (N = 2). They accounted for 8.2% (9/110) of cases with GATA2 deficiency in our cohort and resulted in selective loss of mutant RNA. While for the hotspot mutation (c.351C>G) a splicing error leading to RNA and protein reduction was identified, severe, likely late stage RNA loss without splicing disruption was found for other mutations. Finally, the synonymous mutations did not alter protein function or stability. In summary, synonymousGATA2substitutions are a new common cause of GATA2 deficiency. These findings have broad implications for genetic counseling and pathogenic variant discovery in Mendelian disorders.}},
  author       = {{Kozyra, Emilia J. and Pastor, Victor B. and Lefkopoulos, Stylianos and Sahoo, Sushree S. and Busch, Hauke and Voss, Rebecca K. and Erlacher, Miriam and Lebrecht, Dirk and Szvetnik, Enikoe A. and Hirabayashi, Shinsuke and Pasauliene, Ramunè and Pedace, Lucia and Tartaglia, Marco and Klemann, Christian and Metzger, Patrick and Boerries, Melanie and Catala, Albert and Hasle, Henrik and de Haas, Valerie and Kallay, Krisztian and Masetti, Riccardo and De Moerloose, Barbara and Dworzak, Michael and Schmugge, Markus and Smith, Owen and Stary, Jan and Mejstrikova, Ester and Ussowicz, Marek and Morris, Emma and Singh, Preeti and Collin, Matthew and Derecka, Marta and Göhring, Gudrun and Flotho, Christian and Strahm, Brigitte and Locatelli, Franco and Niemeyer, Charlotte M. and Trompouki, Eirini and Wlodarski, Marcin W.}},
  issn         = {{0887-6924}},
  journal      = {{LEUKEMIA}},
  keywords     = {{WORLD-HEALTH-ORGANIZATION,MYELOID NEOPLASMS,LEUKEMIA,DIFFERENTIATION,CLASSIFICATION,TRANSCRIPTION,EXPRESSION,REVISION,ABSENCE,VARIANT}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{2673--2687}},
  title        = {{Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency}},
  url          = {{http://doi.org/10.1038/s41375-020-0899-5}},
  volume       = {{34}},
  year         = {{2020}},
}

Altmetric
View in Altmetric
Web of Science
Times cited: