| Literature DB >> 28941052 |
Wei Shen1,2, Jennifer M Heeley3, Colleen M Carlston1,2, Rocio Acuna-Hidalgo4, Willy M Nillesen4, Karin M Dent5, Ganka V Douglas6, Kara L Levine6, Pinar Bayrak-Toydemir1,2, Carlo L Marcelis4, Marwan Shinawi7, John C Carey5.
Abstract
De novo, germline variants in DNMT3A cause Tatton-Brown-Rahman syndrome (TBRS). This condition is characterized by overgrowth, distinctive facial appearance, and intellectual disability. Somatic DNMT3A variants frequently occur in hematologic malignances, particularly acute myeloid leukemia. The Arg882 residue is the most common site of somatic DNMT3A variants, and has also been altered in patients with TBRS. Here we present three additional patients with this disorder attributed to DNMT3A 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 DNMT3A variants observed in this disorder and somatic variants in hematological malignancies.Entities:
Keywords: DNMT3A; Tatton-Brown-Rahman syndrome; exome sequencing; hematologic malignancies
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Year: 2017 PMID： 28941052 DOI： 10.1002/ajmg.a.38485
Source DB: PubMed Journal: Am J Med Genet A ISSN： 1552-4825 Impact factor: 2.802