1. The spectrum of DNMT3A variants in Tatton-Brown-Rahman syndrome overlaps with that in hematologic malignancies.
- Author
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Shen W, Heeley JM, Carlston CM, Acuna-Hidalgo R, Nillesen WM, Dent KM, Douglas GV, Levine KL, Bayrak-Toydemir P, Marcelis CL, Shinawi M, and Carey JC
- Subjects
- Codon, DNA Methyltransferase 3A, Female, Genetic Predisposition to Disease, Germ-Line Mutation genetics, Hematologic Neoplasms pathology, Humans, Intellectual Disability pathology, Male, Mutation, Phenotype, DNA (Cytosine-5-)-Methyltransferases genetics, Face physiopathology, Hematologic Neoplasms genetics, Intellectual Disability genetics
- 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., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
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