ABCMdb

PMID: 11755605

Hamilton JW
Gentamicin in pharmacogenetic approach to treatment of cystic fibrosis.
Lancet. 2001 Dec 15;358(9298):2014-6., [PubMed]

Sentences

No. Mutations Sentence Comment

75 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Gly542* THE LANCET ߦ Vol 358 ߦ December 15, 2001 2015 COMMENTARY Effect of CFTR mutations in epithelial cells Lumen Cytoplasm Nucleus Class 4 (eg, R117H) Class 3 (eg, G551D) Class 2 (eg, èc;F508) Class 1 (eg, G542X) Class 5 (eg, A455E) Apical surface Basolateral surface ATP CFTR MSD NBD NBD RD Golgi ER CFTR gene Collectively, the five mutant classes result in little or no functional CFTR expression at the apical surface of epithelial cells, but through different mechanisms. Login to comment 76 ABCC7 p.Gly542* Class 1 mutations are nonsense, frameshift, and splice-junction mutations (such as the nonsense mutation G542X) that cause little or no translation of CFTR mRNA to protein. Login to comment 79 ABCC7 p.Gly551Asp Class 3 mutations result in CFTR proteins that do not function as chloride channels (such as the mutant G551D), or that are not regulated properly in the membrane (eg, by not responding to ATP stimulation through their NBD regions). Login to comment 80 ABCC7 p.Arg117His Class 4 mutations (such as R117H) result in proteins that have altered chloride conductance, mainly due to mutations within or near one of the transmembrane segments. Login to comment 81 ABCC7 p.Ala455Glu Class 5 mutations (such as A455E) reduce synthesis by impairing transcription, causing alternative splicing of mRNA, or causing aminoacid substitutions that alter early steps in protein biogenesis. Login to comment