Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome
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 mutati...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-01-01
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| Series: | Leukemia Research Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213048915000035 |
| _version_ | 1819144446571184128 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jessica M. Schmit |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T12:42:16Z |
| format | Article |
| id | doaj.art-e7e90398f7fd46e3850b777a48c9ca9f |
| institution | Directory Open Access Journal |
| issn | 2213-0489 |
| language | English |
| last_indexed | 2024-12-22T12:42:16Z |
| publishDate | 2015-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Leukemia Research Reports |
| spelling | doaj.art-e7e90398f7fd46e3850b777a48c9ca9f2022-12-21T18:25:25ZengElsevierLeukemia Research Reports2213-04892015-01-0141242710.1016/j.lrr.2015.03.002Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndromeJessica M. Schmit0Daniel J. Turner1Robert A. Hromas2John R. Wingard3Randy A. Brown4Ying Li5Marilyn M. Li6William B. Slayton7Christopher R. Cogle8Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USADivision of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USADivision of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USADivision of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USADivision of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USADivision of Hematopathology, Department of Pathology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USACancer Genetics Laboratory, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USADivision of Hematology and Oncology, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USADivision of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USAHere 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.http://www.sciencedirect.com/science/article/pii/S2213048915000035Congenital thrombocytopeniaFamilial platelet disorderMyelodysplastic syndromesRUNX1 |
| spellingShingle | 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 Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome Leukemia Research Reports Congenital thrombocytopenia Familial platelet disorder Myelodysplastic syndromes RUNX1 |
| title | Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome |
| title_full | Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome |
| title_fullStr | Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome |
| title_full_unstemmed | Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome |
| title_short | Two novel RUNX1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome |
| title_sort | two novel runx1 mutations in a patient with congenital thrombocytopenia that evolved into a high grade myelodysplastic syndrome |
| topic | Congenital thrombocytopenia Familial platelet disorder Myelodysplastic syndromes RUNX1 |
| url | http://www.sciencedirect.com/science/article/pii/S2213048915000035 |
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