|
Neutropenia
|
0.500 |
Biomarker
|
disease |
HPO |
|
|
|
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
LHGDN |
Clinical implications of mutations of neutrophil elastase in congenital and cyclic neutropenia.
|
11846296 |
2001 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We therefore screened GFI1 as a candidate for association with neutropenia in affected individuals without mutations in ELA2 (encoding neutrophil elastase), the most common cause of severe congenital neutropenia (SCN; ref.3).
|
12778173 |
2003 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
LHGDN |
All cases of cyclic neutropenia and most cases of severe congenital neutropenia result from heterozygous germline mutations in the gene encoding neutrophil elastase, ela2.
|
12483111 |
2003 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
LHGDN |
Neutrophil elastase mutations in congenital neutropenia.
|
12745650 |
2003 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
These data demonstrate that impaired survival of bone marrow myeloid progenitor cells, probably driven by expression of mutant NE, is the cellular mechanism responsible for neutropenia in SCN.
|
12763135 |
2003 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mutations associated with neutropenia in dogs and humans disrupt intracellular transport of neutrophil elastase.
|
12897784 |
2003 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
LHGDN |
Most CN mutations fall within predicted transmembrane domains and lead to excessive deposition of NE in granules, whereas SCN mutations usually disrupt the AP3 recognition sequence, resulting in excessive transport to the plasma membrane.
|
15059607 |
2004 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Disease-causing mutations of neutrophil elastase disrupt the interaction with N2N, impair proteolysis of N2N and Notch2, and interfere with Notch2 signaling, suggesting defective proteolysis of an inhibitory form of Notch as an explanation for the alternate switching of cell fates characteristic of hereditary neutropenia.
|
14673143 |
2004 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
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.
|
14962902 |
2004 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
LHGDN |
These observations provide further insight into potential mechanisms by which NE mutations cause neutropenia and suggest that abnormal protein trafficking and accelerated apoptosis of differentiating myeloid cells contribute to the severe SCN phenotype resulting from the G185R mutation.
|
15657182 |
2005 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
LHGDN |
Mutations in the neutrophil elastase gene, ELA2, have been reported in patients with CyN and in those with SCN.
|
16079102 |
2005 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
These observations provide further insight into potential mechanisms by which NE mutations cause neutropenia and suggest that abnormal protein trafficking and accelerated apoptosis of differentiating myeloid cells contribute to the severe SCN phenotype resulting from the G185R mutation.
|
15657182 |
2005 |
|
Neutropenia
|
0.500 |
Biomarker
|
disease |
BEFREE |
Gene targeting of ELA2 has thus far failed to recapitulate neutropenia in mice.
|
17053055 |
2007 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
LHGDN |
Heterozygous mutations of ELA2, encoding the protease neutrophil elastase (NE), cause either autosomal dominant cyclic neutropenia or severe congenital neutropenia (SCN).
|
17436313 |
2007 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
ELA2 mutations have been found in cyclic, sporadic and autosomal dominant neutropenia.
|
17917547 |
2007 |
|
Neutropenia
|
0.500 |
Biomarker
|
disease |
CTD_human |
Heterozygous mutations of ELA2, encoding the protease neutrophil elastase (NE), cause either autosomal dominant cyclic neutropenia or severe congenital neutropenia (SCN).
|
17436313 |
2007 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
A 12-year-old daughter of consanguineous Moroccan parents was diagnosed with cyclic neutropenia, based on a combination of recurrent gingivostomatitis, a fluctuating neutrophil count, and several episodes of severe neutropenia.No ELA2 gene mutations were found.
|
18661496 |
2008 |
|
Neutropenia
|
0.500 |
Biomarker
|
disease |
BEFREE |
Contributions to neutropenia from PFAAP5 (N4BP2L2), a novel protein mediating transcriptional repressor cooperation between Gfi1 and neutrophil elastase.
|
19506020 |
2009 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
He was found to be heterozygous for the M1V variant of the ELA-2 gene that we postulate to be causative for his severe neutropenia
|
21618407 |
2011 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
She had repeated episodes of neutropenia regularly at 3-week intervals and a pathogenic mutation in the ELA2 gene.
|
21161286 |
2011 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l.When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease.Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant.About half the forms of congenital neutropenia with no extra-hematopoietic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations.
|
21595885 |
2011 |
|
Neutropenia
|
0.500 |
Biomarker
|
disease |
BEFREE |
Some ELANE mutations, therefore, appear to cause neutropenia via the production of amino-terminally deleted NE isoforms rather than by altering the coding sequence of the full-length protein.
|
24184683 |
2014 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells.
|
26193632 |
2015 |
|
Neutropenia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The diversity of mutations and clinical outcomes for ELANE-associated neutropenia.
|
25427142 |
2015 |