title: Fanconi anemia-like presentation in an infant with constitutional deletion of 21q including the RUNX1 gene.
abstract: We describe a newborn female with a de novo interstitial deletion of chromosome 21q21.1-22.12 including the RUNX1 gene who had developmental delay, multiple congenital anomalies, tetralogy of Fallot, anemia, and chronic thromobocytopenia requiring frequent platelet transfusions from birth. Because of her physical and hematologic abnormalities, she was tested for Fanconi anemia (FA). Lymphocytes and fibroblasts from this patient demonstrated increased chromosome breakage with exposure to the clastogen mitomycin C, but not, in contrast to most FA patients, to diepoxybutane. Further testing by Western analysis and complementation testing did not show a defect in the function of known Fanconi proteins. Her constitutional deletion was later found to span 13.2 Mb by chromosome microarray analysis, encompassing the RUNX1 gene that has been implicated in thrombocytopenia and predisposition to acute myelogenous leukemia (AML) when in the haploinsufficient state. We compare her phenotype to other individuals with similar 21q deletions and thrombocytopenia, as well as those with FA. We suggest that deletion of RUNX1 or another critical gene within the deleted region may result in chromosomal instability similar to that seen in FA.
authors.affiliation: Seattle Children's Hospital, Washington, USA.
authors.forename: Eleanor S
authors.initials: ES
authors.lastname: Click
authors.forename: Barbara
authors.initials: B
authors.lastname: Cox
authors.forename: Susan B
authors.initials: SB
authors.lastname: Olson
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
authors.forename: Yassmine
authors.initials: Y
authors.lastname: Akkari
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Moreau
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimamura
authors.forename: Darci L
authors.initials: DL
authors.lastname: Sternen
authors.forename: Yajuan J
authors.initials: YJ
authors.lastname: Liu
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Leppig
authors.forename: Dana C
authors.initials: DC
authors.lastname: Matthews
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Parisi
mesh_terms: D019457:Chromosome Breakage / Q000187:drug effects; D002872:Chromosome Deletion; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005199:Fanconi Anemia / Q000175:diagnosis / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D009153:Mutagens / Q000494:pharmacology; D010641:Phenotype
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D009153:Mutagens