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Article Abstract
Germline pathogenic variants in DNMT3A were recently described in patients with overgrowth, obesity, behavioral, and learning difficulties (DNMT3A Overgrowth Syndrome/DOS). Somatic mutations in the DNMT3A gene are also the most common cause of clonal hematopoiesis, and can initiate acute myeloid leukemia (AML). Using whole genome bisulfite sequencing, we studied DNA methylation in peripheral blood cells of 11 DOS patients and found a focal, canonical hypomethylation phenotype, which is most severe with the dominant negative DNMT3A mutation. A germline mouse model expressing the homologous Dnmt3a mutation phenocopies most aspects of the human DOS syndrome, including the methylation phenotype and an increased incidence of spontaneous hematopoietic malignancies, suggesting that all aspects of this syndrome are caused by this mutation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316576 | PMC |
| http://dx.doi.org/10.1038/s41467-021-24800-7 | DOI Listing |
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Article Synopsis
- Tatton-Brown-Rahman syndrome (TBRS) is a genetic condition characterized by excessive growth, learning difficulties, and unique facial characteristics linked to mutations in the DNMT3A gene.
- A case study presented a four-year-old girl with a novel DNMT3A mutation who also experienced immune thrombocytopenic purpura (ITP), a condition that affects blood platelet levels.
- The report highlights the potential connection between TBRS and autoimmune disorders like ITP, suggesting that these health issues should be monitored in TBRS patients, but more research is needed to confirm this link.