title: A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies.
abstract: Hereditary mutations associated with hematologic malignancies are rare. Heterozygous mutations affecting the hematopoietic transcription factor CBFA2 (also AML1/RUNX1) were recently reported to be associated with familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML, MIM 601399). A new 3-generation family with FPD/AML with a novel CBFA2 mutation is described. In this family, AML was diagnosed in a second-generation male. After allogeneic stem cell transplantation from his human leukocyte antigen-identical sister, a donor-derived, genetically identical leukemia developed in the recipient and the donor. Sequencing analysis identified a G-to-T transition within the CBFA2 gene, which involves codon 198, encoding a conserved aspartic acid within the DNA- binding Runt domain. Three of 5 siblings affected with the FPD/AML trait harbored the mutation in a heterozygous form. This experience underscores the necessity of performing mutation analysis of the CBFA2 gene before sibling allogeneic transplantation in families with FPD/AML.
authors.affiliation: Division of Medical Genetics and the Departments of Hematology, Immunology, and Clinical Chemistry, University Medical Center Utrecht, The Netherlands. a.buijs@dmg.azu.nl
authors.forename: A
authors.initials: A
authors.lastname: Buijs
authors.forename: P
authors.initials: P
authors.lastname: Poddighe
authors.forename: R
authors.initials: R
authors.lastname: van Wijk
authors.forename: W
authors.initials: W
authors.lastname: van Solinge
authors.forename: E
authors.initials: E
authors.lastname: Borst
authors.forename: L
authors.initials: L
authors.lastname: Verdonck
authors.forename: A
authors.initials: A
authors.lastname: Hagenbeek
authors.forename: P
authors.initials: P
authors.lastname: Pearson
authors.forename: H
authors.initials: H
authors.lastname: Lokhorst
mesh_terms: D000208:Acute Disease; D000328:Adult; D001791:Blood Platelet Disorders / Q000150:complications / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood / Q000209:etiology / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D014157:Transcription Factors