A mutation in CFTR produces different phenotypes depending on chromosomal background
- 1 November 1993
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 5 (3) , 274-278
- https://doi.org/10.1038/ng1193-274
Abstract
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene but the association between mutation (genotype) and disease presentation (phenotype) is not straightforward. We have been investigating whether variants in the CFTR gene that alter splicing efficiency of exon 9 can affect the phenotype produced by a mutation. A missense mutation, R117H, which has been observed in three phenotypes, was found to occur on two chromosome backgrounds with intron 8 variants that have profoundly different effects upon splicing efficiency. A close association is shown between chromosome background of the R117H mutation and phenotype. These findings demonstrate that the genetic context in which a mutation occurs can play a significant role in determining the type of illness produced.Keywords
This publication has 22 references indexed in Scilit:
- Expression of an abundant alternatively spliced form of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is not associated with a cAMP-activated chloride conductanceHuman Molecular Genetics, 1993
- Genetic basis of variable exon 9 skipping in cystic fibrosis transmembrane conductance regulator mRNANature Genetics, 1993
- The spectrum of cystic fibrosis mutationsTrends in Genetics, 1992
- A cystic fibrosis allele encoding missense mutations in both nucleotide binding folds of the cystic fibrosis transmembrane conductance regulatorHuman Mutation, 1992
- Identification of mutations in exons 1 through 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) geneGenomics, 1991
- Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) geneGenomics, 1991
- A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator proteinNature, 1990
- Multiple mutations in highly conserved residues are found in mildly affected cystic fibrosis patientsCell, 1990
- Identification of the Cystic Fibrosis Gene: Genetic AnalysisScience, 1989
- Recurrent mutations in haemophilia A give evidence for CpG mutation hotspotsNature, 1986