Acute myeloid leukemia-associated DNMT3A p.Arg882His mutation in a patient with Tatton-Brown–Rahman overgrowth syndrome as a constitutional mutation

Rika Kosaki, Hiroshi Terashima, Masaya Kubota, Kenjiro Kosaki

研究成果: Article

19 引用 (Scopus)

抜粋

DNA methylation plays a critical role in both embryonic development and tumorigenesis and is mediated through various DNA methyltransferases. Constitutional mutations in the de novo DNA methyltransferase DNMT3A cause a recently identified Tatton-Brown–Rahman overgrowth syndrome (TBRS). Somatically acquired mutations in DNMT3A are causally associated with acute myeloid leukemia (AML), and p.Arg882His represents the most prevalent hotspot. So far, no patients with TBRS have been reported to have subsequently developed AML. Here, we report a live birth and the survival of a female with the TBRS phenotype who had a heterozygous constitutional DNMT3A mutation at the AML somatic mutation hotspot p.Arg882His in her DNA from peripheral blood and buccal tissue. Her characteristic features at birth included hypotonia, narrow palpebral fissures, ventricular septal defect, umbilical hernia, sacral cyst, Chiari type I anomaly. At the age of 6 years, she exhibited overgrowth (> 3 SD) and round face and intellectual disability. This report represents the first documentation of the same variant (DNMT3A p.Arg882His) as both the constitutional mutation associated with TBRS and the somatic mutation hotspot of AML. The observation neither confirms nor denies the notion that mutations responsible for TBRS and those for AML might share the same mode of action. Larger data sets are required to determine whether TBRS patients with constitutional DNMT3A mutations are at an increased risk for AML.

元の言語English
ページ(範囲)250-253
ページ数4
ジャーナルAmerican Journal of Medical Genetics, Part A
173
発行部数1
DOI
出版物ステータスPublished - 2017 1 1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

フィンガープリント Acute myeloid leukemia-associated DNMT3A p.Arg882His mutation in a patient with Tatton-Brown–Rahman overgrowth syndrome as a constitutional mutation' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用