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.
['Staňo Kozubík|Kateřina|K|', 'Radová|Lenka|L|', 'Pešová|Michaela|M|', 'Réblová|Kamila|K|', 'Trizuljak|Jakub|J|', 'Plevová|Karla|K|', 'Fiamoli|Veronika|V|', 'Gumulec|Jaromír|J|', 'Urbánková|Helena|H|', 'Szotkowski|Tomáš|T|', 'Mayer|Jiří|J|', 'Pospíšilová|Šárka|Š|', 'Doubek|Michael|M|http://orcid.org/0000-0002-1269-6282']
D001706:Biopsy D001791:Blood Platelet Disorders D002675:Child, Preschool D002869:Chromosome Aberrations D050676:Core Binding Factor Alpha 2 Subunit D004252:DNA Mutational Analysis D018450:Disease Progression D005190:Family D005260:Female D020022:Genetic Predisposition to Disease D006801:Humans D059785:Karyotype D007951:Leukemia, Myeloid D009154:Mutation D010976:Platelet Count D020641:Polymorphism, Single Nucleotide
RUNX1 Familial platelet disorder with predisposition to myeloid malignancies Inherited thrombocytopenia