Mosaic tetraploidy and transient GFI1 mutation in a patient with severe chronic neutropenia

This report presents the case of a 15‐year‐old male with severe chronic neutropenia, leukopenia, and persistent tetraploid mosaicism in the bone marrow and peripheral blood. His father had mild neutropenia and bone marrow tetraploidy. Flow cytometric analysis of DNA content peripheral blood showed tetraploidy in 20% of granulocytes and 15% of monocytes. Sequence analysis of the ELA2 gene was normal, but the GFI1 gene exhibited transient appearance of single base changes the coding region and promoter. We speculate that an underlying genetic defect, inherited in an autosomal dominant pattern, leads to both disordered mitosis and neutropenia in this kindred. Pediatr Blood Cancer 2008;50:630–632. © 2006 Wiley‐Liss, Inc.

[1]  T. Vulliamy,et al.  Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. , 2006, Blood.

[2]  Philip S Rosenberg,et al.  The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. , 2005, Blood.

[3]  E. Morava,et al.  Transient progeroid phenotype and lipodystrophy in mosaic polyploidy. , 2006, Clinical dysmorphology.

[4]  S. Kulkarni,et al.  The effect of TERC haploinsufficiency on the inheritance of telomere length. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[5]  B. Smith,et al.  Flow Cytometric DNA Ploidy Analysis of Peripheral Blood From Patients With Sézary Syndrome , 2004 .

[6]  B. Smith,et al.  Flow cytometric DNA ploidy analysis of peripheral blood from patients with sezary syndrome: detection of aneuploid neoplastic T cells in the blood is associated with large cell transformation in tissue. , 2004, American journal of clinical pathology.

[7]  M. Horwitz,et al.  Congenital and acquired neutropenia. , 2004, Hematology. American Society of Hematology. Education Program.

[8]  George Eliopoulos,et al.  Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2 , 2003, Nature Genetics.

[9]  W. Liles,et al.  Cellular and molecular abnormalities in severe congenital neutropenia predisposing to leukemia. , 2003, Experimental hematology.

[10]  M. Freedman,et al.  Severe chronic neutropenia: Treatment and follow‐up of patients in the Severe Chronic Neutropenia International Registry , 2003, American journal of hematology.

[11]  D. Dale,et al.  Mutations in the neutrophil elastase gene in cyclic and congenital neutropenia. , 2001, Current opinion in immunology.

[12]  P G Mori,et al.  Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy. , 2000, Blood.

[13]  R. Hromas,et al.  Characterization of the DNA-binding properties of the myeloid zinc finger protein MZF1: two independent DNA-binding domains recognize two DNA consensus sequences with a common G-rich core , 1994, Molecular and cellular biology.

[14]  B. Wullich,et al.  Mosaic tetraploidy in a liveborn infant with features of the DiGeorge anomaly , 1991, Clinical genetics.

[15]  H. Saal,et al.  Diploid/tetraploid mosaicism in a liveborn infant demonstrable only in the bone marrow: case report and literature review , 1988, Clinical genetics.

[16]  H. Lithell,et al.  Tetraploidy in two sisters with the polycystic ovary syndrome , 1985, Clinical genetics.

[17]  A. Carroll,et al.  Tetraploidy: a report of three live-born infants. , 1984, American journal of medical genetics.