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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dale, D. C. Articles by Horwitz, M. Search for Related Content PubMed PubMed Citation Articles by Dale, D. C. Articles by Horwitz, M. Related Collections Hematopoiesis and Stem Cells Phagocytes Plenary Papers Clinical Trials and Observations Related Letter in Blood Online Social Bookmarking                   What's this? Next Article  Blood, 1 October 2000, Vol. 96, No. 7, pp. 2317-2322 PLENARY PAPER Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia David C. Dale, Richard E. Person, Audrey Anna Bolyard, Andrew G. Aprikyan, Cindy Bos, Mary Ann Bonilla, Laurence A. Boxer, George Kannourakis, Cornelia Zeidler, Karl Welte, Kathleen F. Benson, and Marshall Horwitz From the Divisions of Hematology and Medical Genetics, Department of Medicine and the Markey Molecular Medicine Center, University of Washington School of Medicine, Seattle, WA; St Barnabas Medical Center, West Orange, NJ; University of Michigan, Ann Arbor, MI; University of Ballarat, Ballarat, Australia; and Medizinische Hochschule, Hannover, Germany. Congenital neutropenia and cyclic neutropenia are disorders of neutrophil production predisposing patients to recurrent bacterial infections. Recently the locus for autosomal dominant cyclic neutropenia was mapped to chromosome 19p13.3, and this disease is now attributable to mutations of the gene encoding neutrophil elastase (the ELA2 gene). The authors hypothesized that congenital neutropenia is also due to mutations of neutrophil elastase. Patients with congenital neutropenia, cyclic neutropenia, or Shwachman-Diamond syndrome were referred to the Severe Chronic Neutropenia International Registry. Referring physicians provided hematologic and clinical data. Mutational analysis was performed by sequencing polymerase chain reaction (PCR)-amplified genomic DNA for each of the 5 exons of the neutrophil ELA2 gene and 20 bases of the flanking regions. RNA from bone marrow mononuclear cells was used to determine if the affected patients expressed both the normal and the abnormal transcript. Twenty-two of 25 patients with congenital neutropenia had 18 different heterozygous mutations. Four of 4 patients with cyclic neutropenia and 0 of 3 patients with Shwachman-Diamond syndrome had mutations. For 5 patients with congenital neutropenia having mutations predicted to alter RNA splicing or transcript structure, reverse transcriptase-PCR showed expression of both normal and abnormal transcripts. In cyclic neutropenia, the mutations appeared to cluster near the active site of the molecule, whereas the opposite face was predominantly affected by the mutations found in congenital neutropenia. This study indicates that mutations of the gene encoding neutrophil elastase are probably the most common cause for severe congenital neutropenia as well as the cause for sporadic and autosomal dominant cyclic neutropenia. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Significance of neutrophil elastase mutations versus G-CSF receptor mutations for leukemic progression of congenital neutropenia Mirjam H. A. Hermans, Ivo P. Touw, David C. Dale, and Andrew Aprikyan Blood 2001 97: 2185-2186. [Full Text] [PDF] This article has been cited by other articles: C. Klein Molecular basis of congenital neutropenia Haematologica, October 1, 2009; 94(10): 1333 - 1336. 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Ancliff, R. E. Gale, M. J. Watts, R. Liesner, I. M. Hann, S. Strobel, and D. C. Linch Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia Blood, June 28, 2002; 100(2): 707 - 709. [Abstract] [Full Text] [PDF] A. Valenzuela-Fernandez, T. Planchenault, F. Baleux, I. Staropoli, K. Le-Barillec, D. Leduc, T. Delaunay, F. Lazarini, J.-L. Virelizier, M. Chignard, et al. Leukocyte Elastase Negatively Regulates Stromal Cell-derived Factor-1 (SDF-1)/CXCR4 Binding and Functions by Amino-terminal Processing of SDF-1 and CXCR4 J. Biol. Chem., May 3, 2002; 277(18): 15677 - 15689. [Abstract] [Full Text] [PDF] P. J. Ancliff, R. E. Gale, R. Liesner, I. M. Hann, and D. C. Linch Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease Blood, November 1, 2001; 98(9): 2645 - 2650. 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[Abstract] [Full Text] [PDF]

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