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.
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Kiesewetter, S., Macek, M., Davis, C. et al. A mutation in CFTR produces different phenotypes depending on chromosomal background. Nat Genet 5, 274–278 (1993). https://doi.org/10.1038/ng1193-274
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DOI: https://doi.org/10.1038/ng1193-274
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