ABCMdb

PMID: 22698459

Lubamba B, Dhooghe B, Noel S, Leal T
Cystic fibrosis: insight into CFTR pathophysiology and pharmacotherapy.
Clin Biochem. 2012 Oct;45(15):1132-44. doi: 10.1016/j.clinbiochem.2012.05.034. Epub 2012 Jun 12., [PubMed]

Sentences

No. Mutations Sentence Comment

979 ABCC7 p.Trp1282* For instance, the W1282X, a stop codon mutation, accounts for 48% of CF chromosomes in Ashkenazi Jews [65] and 23% of French Canadian CF chromosomes carry the 621+ 1G>T variant [66,67]. Login to comment 982 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Gly314Glu ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Asp1152His Class Mutation prototypes Consequences Severe CF phenotype I G542X, W1282X, R553X, 3950delT CFTR is not synthesized because of stop codons or splicing defects II F508del, N1303K CFTR is synthesized but in an immature form (only partly glycosylated, misfolded, not released from the endoplasmic reticulum) and is mostly degraded by the ubiquitin-proteasomal pathway III G551D CFTR is synthesized and transported to the plasma membrane, but its activation and regulation by ATP or cAMP are disrupted Milder CF phenotype IV R334W, G314E, R347P, D1152H CFTR is synthesized and expressed at the plasma membrane, but chloride conductance is reduced V 3849+10 kb C>T, 3272-26 A>G CFTR synthesis or processing is partly defective Severe CF phenotype VI 1811+1.6 kb A>G CFTR is synthesized, but membrane stability or conductance of ions other than chloride is reduced Fig. 2. Login to comment 1118 ABCC7 p.Gly551Asp The G551D, a prototype of class III mutation, is the third most common mutation found in patients with CF; however, it accounts for only about 2-3% of cases worldwide. Login to comment 1119 ABCC7 p.Gly551Asp Ivacaftor was shown to stimulate chloride transport in epithelial cells expressing G551D-CFTR [159] which is a severe gating defective mutant with normal expression at the cell membrane. Login to comment 1120 ABCC7 p.Gly551Asp Encouraging data have been collected recently for ivacaftor during a multicentric clinical trial enrolling 39 CF patients who carry at least one copy of the G551D mutation. Login to comment 1131 ABCC7 p.Gly551Asp NS004 was shown to be able to activate wild-type and G551D-CFTR mutant chloride channels [164]. Login to comment