Acute myeloid leukaemia in a case with Tatton-Brown-Rahman syndrome: the peculiarDNMT3AR882 mutation
| Autor: | C. Michel Zwaan, Ans M.W. van den Ouweland, H. Berna Beverloo, Susan T C J M Arentsen-Peters, Iris H.I.M. Hollink, Anja Wagner |
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| Přispěvatelé: | Clinical Genetics, Pediatrics |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mutation Macrocephaly Karyotype Biology medicine.disease_cause medicine.disease Phenotype PTPN11 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Immunology Intellectual disability Genetics medicine Cancer research Epigenetics Myeloid leukaemia medicine.symptom Genetics (clinical) |
| Zdroj: | Journal of Medical Genetics, 54(12), 805-808. BMJ Publishing Group |
| ISSN: | 1468-6244 0022-2593 |
| DOI: | 10.1136/jmedgenet-2017-104574 |
| Popis: | Background Recently a novel syndromic form of overgrowth with intellectual disability and distinct facial features was identified caused by constitutional mutations in the epigenetic regulator DNA-methyltransferase 3A ( DNMT3A ), referred to as Tatton-Brown-Rahman syndrome (TBRS). Somatically acquired mutations in DNMT3A occur in haematological malignancies and are frequently present in acute myeloid leukaemia (AML) affecting in more than 50% the arginine residue at position 882 (R882). To date, additional cases with TBRS have been published but so far none of the reported cases with TBRS developed AML. Methods and results Here we present the first case of TBRS who developed AML at the age of 15 years. Whole-exome sequencing identified a constitutional heterozygous DNMT3A R882C mutation. Our case exhibits macrocephaly, intellectual disability, distinct facial dysmorphism and other recurrent features fitting with the TBRS phenotype. The AML of the myelomonocytic subtype harboured only few additional somatically acquired mutations, that is, an aberrant karyotype and a recurrent PTPN11 mutation. Discussion The peculiarity of the specific R882 mutation in contrast to other DNMT3A mutations is discussed, including the hypothesis of the more aggressive nature of this variant. Our case represents the first evidence of the possible increased risk of the development of haematological malignancies in particular AML in cases with TBRS. |
| Databáze: | OpenAIRE |
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