Transcript analysis of CFTR nonsense mutations in lymphocytes and nasal epithelial cells from cystic fibrosis patients
- 1 January 1995
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 5 (3) , 210-220
- https://doi.org/10.1002/humu.1380050305
Abstract
The mutational effects at the mRNA level were investigated by RT‐PCR analysis of nine different nonsense mutations (Q39X, E60X, R75X, G542X, L719X, Y1092X, R1162X, S1196X, W1282X) and one frameshift mutation (1078delT) within the CFTR gene. With the exception of mutation R1162X, reduced mRNA levels ranging from 30% to less than 5% of the wild type have been observed. In case of the R75X and E60X mutations, the mRNA reduction was accompanied by the appearance of atypical CFTR isoforms. Single exon 3 skipping, as well as joint exon 2 and 3 skipping, was observed in lymphocyte and nasal epithelial mRNA derived from R75X alleles. The analysis of mRNA transcribed from E60X alleles revealed skipping of exon 3 (lymphocytes and nasal epithelial cells) or skipping of exons 3 and 4 (nasal epithelial cells). With the exception of the E60X mutation, no obvious tissue‐specific differences in the splicing pattern and ratios of mutation to wild‐type transcripts were detected between lymphocytes and nasal epithelial cells. In addition to aberrant splicing, the reduction of transcripts is the most common effect of nonsense and frameshift mutations within the CFTR gene.Keywords
This publication has 45 references indexed in Scilit:
- A novel exon in the cystic fibrosis transmembrane conductance regulator gene activated by the nonsense mutation E92X in airway epithelial cells of patients with cystic fibrosis.Journal of Clinical Investigation, 1994
- The Stop Mutation R553X in the CFTR Gene Results in Exon SkippingGenomics, 1994
- A 32-bp deletion (2991del32) in the cystic fibrosis gene associated with CFTR mRNA reductionHuman Mutation, 1994
- Nonsense mutation R1162X of the cystic fibrosis transmembrane conductance regulator gene does not reduce messenger RNA expression in nasal epithelial tissue.Journal of Clinical Investigation, 1993
- A donor splice mutation (405 + 1 G → A) in cystic fibrosis associated with exon skipping in epithelial CFTR mRNAHuman Molecular Genetics, 1993
- A nonsense mutation and exon skipping in the Fanconi anaemia group C geneHuman Molecular Genetics, 1993
- Molecular characterization of a frameshift mutation in exon 19 of the CFTR geneHuman Mutation, 1993
- A new mutation (1078delT) in exon 7 of the CFTR gene in a southern French adult with cystic fibrosisGenomics, 1992
- Three novel mutations in the cystic fibrosis gene detected by chemical cleavage: analysis of variant splicing and a nonsense mutationHuman Molecular Genetics, 1992
- Spectrum of spontaneously occurring mutations in the hprt gene of V79 Chinese hamster cellsJournal of Molecular Biology, 1992