Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome

摘要

Here we report two new RUNX 1 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 RUNX 1 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 RUNX 1 mutations may have exerted a stronger dominant negative effect than either RUNX 1 mutation alone, thus leading to a myeloid malignancy. Highlights ? We report two new RUNX 1 mutations in a patient with thrombocytopenia and MDS. ? We demonstrate that a second hit to RUNX1 results in transformed MDS. ? Allogeneic transplant was successfully used to treat double RUNX1 mutant MDS.