Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia.
707 - 709.
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 semiquantitative polymerase chain reaction, approximately half of his T cells were shown to carry the mutation in contrast to less than 10% of neutrophils. Individual hematopoietic colonies grown from peripheral blood were heterozygous for the mutation or were 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 humans. The normal neutrophil count in the father suggests that the mutant elastase does not have paracrine effects
|Title:||Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia|
|Open access status:||An open access version is available from UCL Discovery|
|Additional information:||DA - 20020701IS - 0006-4971 (Print)LA - engPT - Case ReportsPT - Journal ArticlePT - Research Support, Non-U.S. Gov'tRN - EC 126.96.36.199 (Leukocyte Elastase)SB - AIMSB - IM|
|Keywords:||congenital, Congenital Neutropenia, MH, mosaicism, Mutation, MUTATIONS, nature, neutropenia, neutrophil, Neutrophil Elastase, Adult, Child, Preschool, congenital, DNA Mutational Analysis, enzymology, etiology, Fathers, Female, genetics, Humans, Leukocyte Elastase, Leukopoiesis, Male, Mosaicism, Neutropenia, Neutrophils, Polymerase Chain Reaction, T-Lymphocytes|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Wolfson Institute and Cancer Institute Administration > Cancer Institute > Research Department of Haematology
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health
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