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International Journal of Hematology

, Volume 108, Issue 6, pp 652–657 | Cite as

C-terminal RUNX1 mutation in familial platelet disorder with predisposition to myeloid malignancies

  • Kateřina Staňo Kozubík
  • Lenka Radová
  • Michaela Pešová
  • Kamila Réblová
  • Jakub Trizuljak
  • Karla Plevová
  • Veronika Fiamoli
  • Jaromír Gumulec
  • Helena Urbánková
  • Tomáš Szotkowski
  • Jiří Mayer
  • Šárka Pospíšilová
  • Michael Doubek
Case Report

Abstract

Here we report a C-terminal RUNX1 mutation in a family with platelet disorder and predisposition to myeloid malignancies. We identified the mutation c.866delG:p.Gly289Aspfs*22 (NM_001754) (RUNX1 b-isoform NM_001001890; c.785delG:p.Gly262Aspfs*22) using exome sequencing of samples obtained from eight members of a single family. The mutation found in our pedigree is within exon eight and the transactivation domain of RUNX1. One of the affected individuals developed myelodysplastic syndrome (MDS), which progressed to acute myelogenous leukemia (AML). A search for the second hit which led to the development of MDS and later AML in this individual revealed the PHF6 gene variant (exon9:c.872G > A:p.G291E; NM_001015877), BCORL1 (exon3:c.1111A > C:p.T371P; NM_001184772) and BCOR gene variant (exon4:c.2076dupT:p.P693fs; NM_001123383), which appear to be very likely second hits participating in the progression to myeloid malignancy.

Keywords

Familial platelet disorder with predisposition to myeloid malignancies Inherited thrombocytopenia RUNX1 

Notes

Acknowledgements

Supported by Ministry of Health of the Czech Republic, Grant No. 16-29447A. All rights reserved.

Compliance with ethical standards

Conflict of interest

The authors have had the costs of participating in certain scientific meetings reimbursed by the pharmaceutical industry.

Supplementary material

12185_2018_2514_MOESM1_ESM.xlsx (14 kb)
Supplementary material 1 (XLSX 13 KB)
12185_2018_2514_MOESM2_ESM.xlsx (13 kb)
Supplementary material 2 (XLSX 13 KB)

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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Kateřina Staňo Kozubík
    • 1
  • Lenka Radová
    • 1
  • Michaela Pešová
    • 1
  • Kamila Réblová
    • 1
  • Jakub Trizuljak
    • 1
    • 2
  • Karla Plevová
    • 1
  • Veronika Fiamoli
    • 3
  • Jaromír Gumulec
    • 4
  • Helena Urbánková
    • 5
  • Tomáš Szotkowski
    • 5
  • Jiří Mayer
    • 1
    • 2
  • Šárka Pospíšilová
    • 1
    • 2
  • Michael Doubek
    • 1
    • 2
  1. 1.Central European Institute of Technology (CEITEC), University HospitalMasaryk UniversityBrnoCzech Republic
  2. 2.Department of Internal Medicine, Hematology and Oncology, University HospitalMasaryk UniversityBrnoCzech Republic
  3. 3.Department of Pediatric HematologyUniversity HospitalBrnoCzech Republic
  4. 4.Department of Hematologic OncologyUniversity HospitalOstravaCzech Republic
  5. 5.Department of Hematologic Oncology, University HospitalPalacký UniversityOlomoucCzech Republic

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