Two novel RUNX1 Mutations in a patient with congenital thrombocytopenia that evolved into a High grade myelodysplastic syndrome

Publication date: Available online 3 April 2015 Source:Leukemia Research Reports Author(s): Jessica M. Schmit , Daniel J. Turner , Robert A. Hromas , John R. Wingard , Randy A. Brown , Ying Li , Marilyn M. Li , William B. Slayton , Christopher R. Cogle 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, c.837G>A, was a nucleotide base substitution from guanine to adenine within exon 8, resulting in a nonsense mutation of amino acid tryptophan (W) to a premature stop codon (X) (p.W279X) 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, c.422_423insAAGGCC, was an in-frame six nucleotide base pair insertion in exon 5 of the RUNX1 gene, which is predicted to result in an insertion of an arginine (R) and proline (P) (p.S141_A142insRP) in the DNA-binding runt homology domain (RHD) of the Runx1 protein. 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 (e.g., CEBPA, FLT3, NPM1, PDGFR) was found using routine genetic screening, it is speculated that the combined effect of these two RUNX1 mutations may have exerted a stronger dominant nega...
Source: Leukemia Research Reports - Category: Hematology Source Type: research