ABCMdb

PMID: 9708232

Davidson DJ, Porteous DJ
Genetics and pulmonary medicine. 1. The genetics of cystic fibrosis lung disease.
Thorax. 1998 May;53(5):389-97., [PubMed]

Sentences

No. Mutations Sentence Comment

16 ABCC7 p.Arg553* ABCC7 p.Gly480Cys Mutations in CFTR may result in: (1) defective CFTR production, such as R553X, due to unstable mRNA and/or premature protein truncation, (2) defective processing of CFTR, such as F508 or G480C, where the mutant protein is not processed to its mature glycosylated form and is not correctly localised to the apical membrane, but is retained in the endoplasmic reticulum and degraded. Login to comment 17 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Gly480Cys However, under permissive conditions in vitro, such as reduced temperature, correct localisation of mature protein can occur where it can function normally (in the case of G480C), or suboptimally (in the case of F508), or (3) defective ion channel function, such as G551D or R117H, in which case some of the mutant protein becomes correctly localised but results in either very little residual function (in the case of G551D) or a substantially reduced level of ion transport (in the case of R117H). Login to comment 24 ABCC7 p.Gly551Asp ABCC7 p.Arg117His The G551D mutation, although also "severe" and conferring pancreatic insuYciency, is observed to be associated with a much lower incidence of meconium ileus, while the R117H mutation is a "mild" mutation in which pancreatic suYciency is generally observed. Login to comment 28 ABCC7 p.Arg117His ABCC7 p.Arg117His Furthermore, individuals carrying the R117H allele are typically more severely aVected if the R117H mutation is in cis with the 5T polymorphism as opposed to the 7T variant, the associated IVS8-T affecting the amount of already functionally impaired CFTR that is correctly spliced to influence the phenotype.7 Thus, detailed studies of the pathophysiological consequences of diVerent mutations and splicing abnormalities have provided some insight into the eVects of specific alterations in the quality or quantity of CFTR and it has been possible to correlate the level of CFTR function with phenotype in an organ specific manner. Login to comment