ABCMdb

PMID: 14534332

Lukacs GL, Durie PR
Pharmacologic approaches to correcting the basic defect in cystic fibrosis.
N Engl J Med. 2003 Oct 9;349(15):1401-4., 2003-10-09 [PubMed]

Sentences

No. Mutations Sentence Comment

31 ABCC7 p.Trp1282* ABCC7 p.Arg553* However, almost 60 percent of Ashkenazi Jewish patients with cystic fibrosis carry at least one copy of a nonsense gene alteration (e.g., R553X, G6542X, or W1282X). Login to comment 33 ABCC7 p.Gly551Asp Depending on the location and the nature of the mu- tatedaminoacidresidue,missensemutationshave pleiotropicfunctionalconsequences.Someincrease the disposal and degradation of CFTR at the cell surface or interfere with its constitutive recycling to the cell membrane.Othersselectivelyimpairthe activationofionconductanceofCFTR(e.g.,G551D) attheplasmamembrane.Althoughindividualmis- sense mutations are rare, they collectively constitute 30 to 35 percent of all CFTR mutations. Login to comment 49 ABCC7 p.Gly551Asp For personal use only. No other uses without permission. Copyright (c) 2003 Massachusetts Medical Society. All rights reserved. , 20031404 PERSPECTIVE Finally, high-throughput screening of large libraries of compounds with the use of a cell-based functional assay has recently led to the identifica- tionofsmallmoleculesthatcancorrecttheplasma- membrane channel activity of G551D and ∆F508 CFTR at very low concentrations.2 Although the clinical applications of these exciting studies will require substantial investments of time, work, and money, they demonstrate the potential value of this approach for identifying pharmacologic agents that will correct the cellular phenotype in cystic fibrosis and other diseases that are caused by misfolding. Login to comment