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

• Autoři: STAŇO KOZUBÍK Kateřina; RADOVÁ Lenka; PEŠOVÁ Michaela; RÉBLOVÁ Kamila; TRIZULJAK Jakub; PLEVOVÁ Karla; FIAMOLI Veronika; GUMULEC J.; URBANKOVA H.; SZOTKOWSKI T.; MAYER Jiří; POSPÍŠILOVÁ Šárka; DOUBEK Michael
• Rok publikování: 2018
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: International journal of hematology
• Fakulta / Pracoviště MU: Středoevropský technologický institut
• www: https://link.springer.com/article/10.1007%2Fs12185-018-2514-3
• Doi: http://dx.doi.org/10.1007/s12185-018-2514-3
• Klíčová slova: Familial platelet disorder with predisposition to myeloid malignancies; Inherited thrombocytopenia; RUNX1
• Popis: 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.

Související projekty

• Vyhledávání mutací predisponujících k familiárním hematologickým a onkologickým onemocněním