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Prepublished online as a Blood First Edition Paper on May 24, 2002; DOI 10.1182/blood-2002-01-0060. This Article Full Text (PDF) All Versions of this Article: 2002-01-0060v1 100/2/707    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 Ancliff, P. J Articles by Linch, D. C Search for Related Content PubMed PubMed Citation Articles by Ancliff, P. J Articles by Linch, D. C Social Bookmarking                   What's this? Submitted January 9, 2002 Accepted March 1, 2002 Paternal Mosaicism Proves the Pathogenic Nature of Mutations in Neutrophil Elastase in Severe Congenital Neutropenia Phil J Ancliff*, Rosemary E Gale, Michael J Watts, Ri Liesner, Ian M Hann, Stephan Strobel, and David C Linch Haematology, University College London, London, United Kingdom; Haematology, Great Ormond Street Children's Hospital, London, United Kingdom Haematology, University College London, London, United Kingdom Haematology, Great Ormond Street Children's Hospital, London, United Kingdom Immunology, Great Ormond Street Children's Hospital, London, United Kingdom * Corresponding author; email: p.ancliff{at}ucl.ac.uk. Heterozygous mutations in neutrophil elastase have been detected in many sporadic cases of congenital neutropenia. However, a convincing pathogenetic mechanism has not been established and it is unclear whether the effects of the mutant enzyme occur within the cell of production or are paracrine in nature. The healthy father of a patient was demonstrated to be mosaic for his daughter's Cys42Arg elastase mutation. Using semi-quantitative PCR, approximately half of his T-cells were shown to carry the mutation in contrast to <10% of neutrophils. Individual hematopoietic colonies grown from peripheral blood were heterozygous for the mutation or homozygous wild-type. These results demonstrate that precursors containing the mutation are selectively lost during myelopoiesis or fail to develop into neutrophils. This is the first in vivo confirmation of the pathogenic nature of elastase mutations in man. The normal neutrophil count in the father suggests that the mutant elastase does not have paracrine effects. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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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