• Media type: E-Article
  • Title: The spectrum of DNMT3A variants in Tatton–Brown–Rahman syndrome overlaps with that in hematologic malignancies
  • Contributor: Shen, Wei; Heeley, Jennifer M.; Carlston, Colleen M.; Acuna‐Hidalgo, Rocio; Nillesen, Willy M.; Dent, Karin M.; Douglas, Ganka V.; Levine, Kara L.; Bayrak‐Toydemir, Pinar; Marcelis, Carlo L.; Shinawi, Marwan; Carey, John C.
  • Published: Wiley, 2017
  • Published in: American Journal of Medical Genetics Part A, 173 (2017) 11, Seite 3022-3028
  • Language: English
  • DOI: 10.1002/ajmg.a.38485
  • ISSN: 1552-4833; 1552-4825
  • Keywords: Genetics (clinical) ; Genetics
  • Origination:
  • Footnote:
  • Description: <jats:sec><jats:label /><jats:p>De novo, germline variants in <jats:italic>DNMT3A</jats:italic> cause Tatton–Brown–Rahman syndrome (TBRS). This condition is characterized by overgrowth, distinctive facial appearance, and intellectual disability. Somatic <jats:italic>DNMT3A</jats:italic> variants frequently occur in hematologic malignances, particularly acute myeloid leukemia. The Arg882 residue is the most common site of somatic <jats:italic>DNMT3A</jats:italic> variants, and has also been altered in patients with TBRS. Here we present three additional patients with this disorder attributed to <jats:italic>DNMT3A</jats:italic> germline variants that disrupt the Arg882 codon, suggesting that this codon may be a germline mutation hotspot in this disorder. Furthermore, based on the investigation of previously reported variants in patients with TBRS, we found overlap in the spectrum of <jats:italic>DNMT3A</jats:italic> variants observed in this disorder and somatic variants in hematological malignancies.</jats:p></jats:sec>