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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4119-4125. Prepublished online as a Blood First Edition Paper on February 12, 2004; DOI 10.1182/blood-2003-10-3518. This Article Full Text (PDF) All Versions of this Article: 2003-10-3518v1 103/11/4119    most recent Alert me when this article is cited Alert me if a correction is posted 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 Bellanne-Chantelot, C. Articles by Donadieu, J. Search for Related Content PubMed PubMed Citation Articles by Bellanne-Chantelot, C. Articles by Donadieu, J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted October 15, 2003 Accepted February 4, 2004 Mutations in the ELA2 gene correlate with more severe expression of neutropenia: A study of 81 patients from the French Neutropenia Register Christine Bellanne-Chantelot*, Severine Clauin, Thierry Leblanc, Bruno Cassinat, Fernando Rodrigues-Lima, Sandrine Beaufils, Christelle Vaury, Mohamed Barkaoui, Odile Fenneteau, Micheline Maier-Redelsperger, Christine Chomienne, and Jean Donadieu Laboratoire Embryologie Pathologique et de Cytogenetique, Hopital Saint Antoine, Paris, France; Laboratoire de Biologie Moleculaire, Hopital Saint Antoine, Paris, France Laboratoire de Biologie Moleculaire, Hopital Saint Antoine, Paris, France Service Hematologie Pediatrique, Hopital Saint Louis, Paris, France Laboratoire de Biologie Cellulaire Hematopoietique, Service de Medecine Nucleaire, Inserm E0-03, Hopital Saint Louis, Paris, France CNRS UMR 7000, Faculte de Medecine Pitie-Salpetriere, Paris, France Service Hemato-Oncologie Pediatrique, Hopital Trousseau, Paris, France Laboratoire Hematologie, Hopital Robert Debre, Paris, France * Corresponding author; email: christine.bellanne{at}sat.ap-hop-paris.fr. Heterozygous mutations of the gene encoding neutrophil elastase (ELA2) have been associated with cyclic neutropenia (CN) and severe congenital neutropenia (SCN). To date, 30 different mutations have been reported, but no correlation has been found with the degree of neutropenia. To address this issue, we analyzed the clinical, hematological and molecular characteristics of 81 unrelated patients with SCN (n=54) or CN (n=27). We identified mutations in 31 patients, two-thirds of whom had sporadic forms. Familial cases were consistent with dominant inheritance. Seventeen novel mutations were identified, showing that the mutational spectrum encompasses not only the region encoding the mature enzyme but also the prodomains and promoter region. Genotype-phenotype analysis strongly suggested that ELA2 mutations correlate with more severe expression of neutropenia, specifically in patients diagnosed with SCN. This study underlines the importance of ELA2 molecular screening to identify patients who may be at particular risk of severe bacterial infections and/or acute myeloid leukaemia/myelodysplasia. By phenotypic analysis of affected relatives and carriers of the same ELA2 mutations, we showed that the expression of neutropenia in CN and SCN may be either homogeneous or variable according to the type of mutations, suggesting different pathogenetic mechanisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Neutrophil elastase and neutropenia David C. Dale Blood 2004 103: 3993-3994. [Full Text] [PDF] This article has been cited by other articles: S. J. Salipante, M. E. B. Rojas, B. Korkmaz, Z. Duan, J. Wechsler, K. F. Benson, R. E. Person, H. L. Grimes, and M. S. 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[Abstract] [Full Text] [PDF] N. Berliner Lessons from congenital neutropenia: 50 years of progress in understanding myelopoiesis Blood, June 15, 2008; 111(12): 5427 - 5432. [Abstract] [Full Text] [PDF] D. S. Grenda, M. Murakami, J. Ghatak, J. Xia, L. A. Boxer, D. Dale, M. C. Dinauer, and D. C. Link Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis Blood, December 15, 2007; 110(13): 4179 - 4187. [Abstract] [Full Text] [PDF] M. Andersson, J. Karlsson, G. Carlsson, and K. Putsep Expression of granule-associated proteins in neutrophils from patients with severe congenital neutropenia Blood, October 1, 2007; 110(7): 2772 - 2773. [Full Text] [PDF] R. Badolato, M. Donini, G. Savoldi, and S. Dusi Response: ELA2 genotype-phenotype correlation to be expected in patients with severe congenital neutropenia Blood, October 1, 2007; 110(7): 2773 - 2774. [Full Text] [PDF] M. Donini, S. Fontana, G. Savoldi, W. 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