title: Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome.
abstract: Here we report two new RUNX1 mutations in one patient with congenital thrombocytopenia that transformed into a high grade myelodysplastic syndrome with myelomonocytic features. The first mutation was a nucleotide base substitution from guanine to adenine within exon 8, resulting in a nonsense mutation in the DNA-binding inhibitory domain of the Runx1 protein. This nonsense mutation is suspected a de novo germline mutation since both parents are negative for the mutation. The second mutation identified was an in-frame six nucleotide base pair insertion in exon 5 of the RUNX1 gene, which is predicted to result in an insertion in the DNA-binding runt homology domain (RHD). This mutation is believed to be a somatic mutation as it was mosaic before allogeneic hematopoietic cell transplantation and disappeared after transplant. As no other genetic mutation was found using genetic screening, it is speculated that the combined effect of these two RUNX1 mutations may have exerted a stronger dominant negative effect than either RUNX1 mutation alone, thus leading to a myeloid malignancy.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Schmit
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Turner
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hromas
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Wingard
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Brown
authors.affiliation: Division of Hematopathology, Department of Pathology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Marilyn M
authors.initials: MM
authors.lastname: Li
authors.affiliation: Division of Hematology and Oncology, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Slayton
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cogle
keywords: Congenital thrombocytopenia; Familial platelet disorder; Myelodysplastic syndromes; RUNX1