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The spectrum of DNMT3A variants in Tatton-Brown-Rahman syndrome overlaps with that in hematologic malignancies.
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.
Affiliation
  • Shen W; Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah.
  • Heeley JM; ARUP Laboratories, Salt Lake City, Utah.
  • Carlston CM; Mercy Kids Genetics, Mercy Hospital St. Louis, St Louis, Missouri.
  • Acuna-Hidalgo R; Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah.
  • Nillesen WM; ARUP Laboratories, Salt Lake City, Utah.
  • Dent KM; Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
  • Douglas GV; Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
  • Levine KL; Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah.
  • Bayrak-Toydemir P; GeneDx, Gaithersburg, Maryland.
  • Marcelis CL; GeneDx, Gaithersburg, Maryland.
  • Shinawi M; Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah.
  • Carey JC; ARUP Laboratories, Salt Lake City, Utah.
Am J Med Genet A ; 173(11): 3022-3028, 2017 Nov.
Article in En | MEDLINE | ID: mdl-28941052
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hematologic Neoplasms / DNA (Cytosine-5-)-Methyltransferases / Face / Intellectual Disability Limits: Female / Humans / Male Language: En Journal: Am J Med Genet A Journal subject: GENETICA MEDICA Year: 2017 Document type: Article Country of publication: Estados Unidos

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hematologic Neoplasms / DNA (Cytosine-5-)-Methyltransferases / Face / Intellectual Disability Limits: Female / Humans / Male Language: En Journal: Am J Med Genet A Journal subject: GENETICA MEDICA Year: 2017 Document type: Article Country of publication: Estados Unidos