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


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.

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

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Correspondence to Michael Doubek.

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

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Staňo Kozubík, K., Radová, L., Pešová, M. et al. C-terminal RUNX1 mutation in familial platelet disorder with predisposition to myeloid malignancies. Int J Hematol 108, 652–657 (2018).

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  • Familial platelet disorder with predisposition to myeloid malignancies
  • Inherited thrombocytopenia
  • RUNX1