|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
NK cells isolated from patients with WHIM syndrome carry gain-of-function (GOF) mutations in CXCR4 (CXCR4<sup>R334X</sup>).
|
31231387 |
2019 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
A nonsense mutation (C-->T) truncating the CXC chemokine receptor 4 (CXCR4) C-terminal cytoplasmic tail domain occurred at nucleotide position 1000(R334X) of the CXCR4 gene in one allele of the patient was identified, and the person was diagnosed as having WHIM syndrome.
|
19476565 |
2009 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
Taken together, these results have revealed a pivotal role for GRK3 in regulating CXCR4 attenuation and have provided a mechanistic link between the GRK3 pathway and the CXCR4-related WHIM(WT) disorder.
|
18274673 |
2008 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
In this review, we discuss of CXCR4 receptor properties and signaling in health and diseases, focusing on the WHIM syndrome, an inherited immunodeficiency caused by mutations of the CXCR4 gene.
|
27363619 |
2016 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
HPV infection has severe effects on patients who display selective susceptibility to the virus in the context of primary immunodeficiencies, such as the warts, hypogammaglobulinemia, infections, and myelokathexis syndrome, which is caused by dysfunctions of CXCR4, the receptor for the CXCL12 chemokine.
|
26967480 |
2016 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Thus, CXCR4 (L329fs) appears to be a de novo autosomal dominant frame-shift gain-of-function mutation that like other carboxy-terminus mutations causes WHIM syndrome.
|
27059040 |
2016 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Fewer patients with MYD88(L265P) and CXCR4(WHIM/FS or NS) vs MYD88(L265P)CXCR4(WT) presented with adenopathy (P < .01), further delineating differences in disease tropism based on CXCR4 status.
|
24553177 |
2014 |
|
WHIM syndrome
|
1.000 |
CausalMutation
|
disease |
CLINVAR |
Chromothriptic cure of WHIM syndrome.
|
25662009 |
2015 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
Low-level Cxcr4-haploinsufficient HSC engraftment is sufficient to correct leukopenia in WHIM syndrome mice.
|
31687976 |
2019 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Heterozygous truncating mutations in CXCR4 have been identified as a cause of WHIM syndrome (warts, hypogammaglobulinemia, immunodeficiency and myelokathexis).
|
20226738 |
2010 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Together, our data provide further evidence that CXCR4(R334X) is a gain-of-function mutation, and support clinical evaluation of AMD3100 as mechanism-based treatment in patients with WHIM syndrome.
|
21070597 |
2011 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Accordingly, like CXCR4(R334X), the most common truncation mutation in WHIM syndrome, CXCR4(E343K) mediated approximately 2-fold increased signaling in calcium flux and chemotaxis assays relative to wild-type CXCR4; however, CXCR4(E343K) had a reduced effect on blocking normal receptor down-regulation from the cell surface.
|
22596258 |
2012 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
CXCR4 mutations in WHIM syndrome: a misguided immune system?
|
15661033 |
2005 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
As a result we can expect to identify markers of the WHIM syndrome, as well as other disorders with WHIM-like features that are associated with dysfunctions of the CXCL12/CXCR4 axis.
|
21178277 |
2010 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
Based on these in vitro results, we conclude that CXCR4 nanobodies hold significant potential as alternative therapeutics for CXCR4-associated diseases such as WHIM syndrome.
|
28768817 |
2017 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Moreover, excessive neutrophil retention in hematopoietic tissue resulting from a constitutively active CXCR4 mutation in zebrafish warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is partially rescued by the inhibitory Rac2 mutation.
|
22014524 |
2011 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
WHIM syndrome-associated CXCR4 truncation mutants lacking the S346/347 phosphosite and the recently identified E343K WHIM mutant displayed strongly impaired phosphorylation at S324/325 and S338/339 as well as reduced CXCL12-induced receptor internalization.
|
23734232 |
2013 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
Potential involvement of this novel motif in cancer metastasis and other CXCR4-associated disorders such as warts, hypogammaglobulinemia, infections and myelokathexis (WHIM) syndrome is discussed.
|
17270027 |
2007 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The identification of mutations in CXCR4 in individuals with WHIM syndrome represents the first example of aberrant chemokine receptor function causing human disease and suggests that the receptor may be important in cell-mediated immunity to HPV infection.
|
12692554 |
2003 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
These mice provide a model to decipher the role of CXCR4 desensitization in the homeostasis of B and T cells and to investigate which manifestations of patients with WHIM syndrome may be overcome by dampening the gain of CXCR4 function.
|
22438253 |
2012 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
Recently, Plerixafor has been suggested as a treatment for WHIM syndrome due to its efficacy as a CXCR4 antagonist, closing the translational research loop.
|
24111611 |
2014 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
The identification of chemokine receptor CXCR4 as the causative gene of WHIM syndrome yields new interest in the study of this disease as a model for the comprehension of CXCR4 biology in humans and highlights the importance of the chemokine network for inducing effective immune responses and governing leukocyte trafficking.
|
14612668 |
2003 |
|
WHIM syndrome
|
1.000 |
GermlineCausalMutation
|
disease |
ORPHANET |
The identification of mutations in CXCR4 in individuals with WHIM syndrome represents the first example of aberrant chemokine receptor function causing human disease and suggests that the receptor may be important in cell-mediated immunity to HPV infection.
|
12692554 |
2003 |
|
WHIM syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
Since CXCR4 and its ligand CXCL12 play an important role in a variety of infectious, inflammatory, autoimmune, and malignant diseases, the study of WHIM syndrome provides important insights into both the physiologic and disease roles of these molecules.
|
30565238 |
2019 |
|
WHIM syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Sequencing the CXCR4 gene revealed a c.1013C > G sequence variant suggesting WHIM syndrome.
|
17087743 |
2007 |