ABCMdb

PMID: 20166764

Becq F
Cystic fibrosis transmembrane conductance regulator modulators for personalized drug treatment of cystic fibrosis: progress to date.
Drugs. 2010 Feb 12;70(3):241-59. doi: 10.2165/11316160-000000000-00000., [PubMed]

Sentences

No. Mutations Sentence Comment

64 ABCC7 p.Asn189Lys Instead, a novel missense mutation N189K was identified in a Chinese patient. Login to comment 67 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* [25,26] Besides F508del, other frequent mutations are found in North African CF patients, in particular W1282X, G542X, R1162X and N1303K. Login to comment 97 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* Class I includes nonsense, frame shift and splice site mutations (e.g. stop mutations: G542X, R553X, W1282X) leading to unstable transcripts and failure of CFTR translation. Login to comment 102 ABCC7 p.Gly551Asp ABCC7 p.Gly1349Asp [28,35] For class III mutants (e.g. G551D, G1349D), no or reduced activation of the CFTR chloride function at the plasma membrane also leads to epithelial Cl- impermeability and to a severe disease as for the first two categories. Login to comment 103 ABCC7 p.Arg117His ABCC7 p.Arg334Trp [33,36,37] With a class IV mutation (e.g. R117H, R334W, R234P), CFTR processing to the apical membrane and regulation by cAMP and cAMP-dependent protein kinase (PKA) are not affected. Login to comment 105 ABCC7 p.Pro574His ABCC7 p.Ala455Glu [38] Class V mutations (e.g. A455E, P574H) are responsible for the production of functional proteins with normal Cl-channel activity and regulation, but at a reduced rate of synthesis. Login to comment 133 ABCC7 p.Trp1282* ABCC7 p.Gly542* [47] In a prospective phase II clinical trial on CF patients selected for expressing CFTR variants with a class I mutation (G542X, W1282X), oral administration of ataluren reduced the epithelial electrophysiological abnormalities caused by CFTR channel dysfunction. Login to comment 136 ABCC7 p.Trp1282* ABCC7 p.Arg1162* A phase IIa study with ataluren in France was intended to evaluate activity, safety and pharmacokinetic observations in children with nonsense mutation (WG542X, W1282X, R1162X). Login to comment 209 ABCC7 p.Gly551Asp ABCC7 p.Gly1349Asp ABCC7 p.Asp1152His [76] Similar effects were observed for G551D, G1349D and D1152H mutants. Login to comment 211 ABCC7 p.Gly551Asp [76] MPB agents are direct activators of wt-CFTR, class II (F508del) and class III (G551D) mutants. Login to comment 245 ABCC7 p.Gly551Asp [90] The therapeutic potential in CF of benzoquinoliziniums was suggested following studies conducted on mutated CFTR with class II (F508del) and class III (G551D) CF mutations. Login to comment 246 ABCC7 p.Gly551Asp [80,81] Similarly, trifluoromethylphenylben- zamine activated the mutant G551D with good affinity. Login to comment 249 ABCC7 p.Gly551Asp [64] VX770 increases the open probability and Cl-conductance of G551D-CFTR channels in vitro. Login to comment 250 ABCC7 p.Gly551Asp An ongoing phase IIa study of VX770 in G551D patients is being conducted to evaluate safety, pharmacokinetics and biomarkers of CFTR activity (figure 3). Login to comment