Premium
Fanconi anemia‐like presentation in an infant with constitutional deletion of 21q including the RUNX1 gene
Author(s) -
Click Eleanor S.,
Cox Barbara,
Olson Susan B.,
Grompe Markus,
Akkari Yassmine,
Moreau Lisa A.,
Shimamura Akiko,
Sternen Darci L.,
Liu Yajuan J.,
Leppig Kathleen A.,
Matthews Dana C.,
Parisi Melissa A.
Publication year - 2011
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.34024
Subject(s) - fanconi anemia , haploinsufficiency , biology , runx1 , genetics , chromosome instability , cancer research , chromosome , phenotype , gene , haematopoiesis , stem cell , dna repair
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. © 2011 Wiley‐Liss, Inc.