|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
We report the results of an observational study investigating its effects in CF patients with non-G551D gating mutations.
|
29685811 |
2019 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
We randomly assigned 39 adults with cystic fibrosis and at least one G551D-CFTR allele to receive oral VX-770 every 12 hours at a dose of 25, 75, or 150 mg or placebo for 14 days (in part 1 of the study) or VX-770 every 12 hours at a dose of 150 or 250 mg or placebo for 28 days (in part 2 of the study).
|
21083385 |
2010 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
We generated G551D CF mice transgenically expressing the human CFTR gene in two tissue compartments previously demonstrated to mediate a CFTR-dependent inflammatory response: lung epithelium and alveolar macrophages.
|
11978765 |
2002 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation.
|
22047557 |
2011 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
We conducted a longitudinal cohort study in 2012-2013 in G551D CF patients age 6 and older with no prior exposure to ivacaftor.
|
24927234 |
2014 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
We conclude that G551D- and G1349D-CFTR have distinct pharmacological profiles and speculate that drug therapy for CF is likely to be mutation-specific.
|
16311240 |
2006 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
We also showed a similar pharmacological effect in nasal cells freshly isolated from a delF508/G551D CF patient.
|
11739639 |
2001 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
VX-770 also increased Cl(-) secretion in cultured human CF bronchial epithelia (HBE) carrying the G551D gating mutation on one allele and the F508del processing mutation on the other allele by approximately 10-fold, to approximately 50% of that observed in HBE isolated from individuals without CF.
|
19846789 |
2009 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
Variability of sweat chloride concentration in subjects with cystic fibrosis and G551D mutations.
|
26996268 |
2017 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
This study analyzed plasma fatty acid levels and urine prostaglandin E metabolites (PGE-M) in 40 subjects with CF participating in the G551D observational (GOAL) study who demonstrated response to the medication by a significant decrease in sweat Cl levels.
|
27473897 |
2017 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
This randomized, double-blind, placebo-controlled trial evaluated ivacaftor in patients with cystic fibrosis aged 6-11 years with a G551D-CFTR mutation on at least one allele.
|
23590265 |
2013 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
This pilot study evaluated the effect of short- and long-term ivacaftor treatment on hyperpolarized <sup>3</sup>He-magnetic resonance imaging (MRI)-defined ventilation defects in patients with cystic fibrosis aged ≥12years with a G551D-CFTR mutation.
|
28132845 |
2017 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The present study characterized in a sample of patients with an established clinical diagnosis of CF (asthma, repeated bronchopneumonia, disorders of nutritional status, etc.) the most frequent mutation (deltaF508) in the North region of Brazil and is also the first report of the G551D mutation.
|
15665983 |
2005 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The potentiator VX-770 was the first CFTR modulator approved by the FDA for treatment of CF patients with the gating mutation G551D.
|
27402691 |
2016 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The potentiator VX-770 (ivacaftor/KALYDECO™) targets defective gating of CFTR and has been approved for treatment of cystic fibrosis (CF) subjects carrying G551D, S1251N or one of 8 other mutations.
|
27160424 |
2016 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The potentiator Kalydeco™ (also known as Ivacaftor or VX-770), developed by Vertex Pharmaceuticals, has been recently approved by the US FDA and the European Medicines Agency (EMA) for the treatment of CF patients carrying at least one CFTR allele with the p.Gly551Asp mutation (2-5 % of all patients).
|
23757197 |
2013 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The potentiator ivacaftor (VX-770) is approved for treating CF patients with G551D and other gating mutations.
|
27707539 |
2017 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The most common mutations in CFTR are a deletion of a phenylalanine residue at position 508 (ΔF508-CFTR, 70-80 % of CF phenotypes) and a Gly551Asp substitution (G551D-CFTR, 4-5 % of alleles), which lead to decreased or almost abolished Cl(-) channel function, respectively.
|
26874684 |
2016 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The mild clinical course of a patient with cystic fibrosis is presented who inherited the two mutations Gly551----Asp and Arg553----Stop in the cystic fibrosis transmembrane conductance regulator gene.
|
1376182 |
1992 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The marked success of ivacaftor both in clinical trials and in post-licensing evaluation studies in treating patients with G551D and other gating mutations has greatly encouraged the ongoing development of similar therapies that can directly target the underlying cause of CF.
|
26091951 |
2015 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) potentiator ivacaftor (Kalydeco®) improves clinical outcome in G551D cystic fibrosis (CF) patients.
|
28445004 |
2017 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The class III CF mutations G551D and G1349D are located within the "signature" sequence LSGGQ and LSHGH of NBD1 and NBD2, respectively.
|
15163550 |
2004 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The G551D Observational Study enrolled a longitudinal observational cohort of US patients with CF aged 6 years and older with at least 1 copy of the G551D mutation.
|
25425629 |
2015 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The G551D mutation is reasonably common in the CF patient population and produces a CFTR protein that localizes normally to the plasma membrane, but fails to open in response to cellular cues.
|
24004658 |
2013 |
|
rs75527207
|
|
Cystic Fibrosis
|
|
0.900 |
GeneticVariation
|
BEFREE |
The G551D CFTR mutation is the third most common CF disease-causing mutation, in which the CFTR protein localizes to the epithelial cell membrane but has defective gating.
|
23616952 |
2013 |