A mutation in CFTR produces different phenotypes depending on chromosomal background

S. Kiesewetter, M. Macek, C. Davis, S. M. Curristin, C. S. Chu, C. Graham, A. E. Shrimpton, S. M. Cashman, L. C. Tsui, J. Mickle, J. Amos, W Edward Jr. Highsmith, A. Shuber, D. R. Witt, R. G. Crystal, G. R. Cutting

Research output: Contribution to journalArticle

321 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)274-278
Number of pages5
JournalNature Genetics
Volume5
Issue number3
DOIs
StatePublished - 1993
Externally publishedYes

Fingerprint

Phenotype
Mutation
Regulator Genes
Chromosomes
Cystic Fibrosis Transmembrane Conductance Regulator
Missense Mutation
Cystic Fibrosis
Introns
Exons
Genotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Kiesewetter, S., Macek, M., Davis, C., Curristin, S. M., Chu, C. S., Graham, C., ... Cutting, G. R. (1993). A mutation in CFTR produces different phenotypes depending on chromosomal background. Nature Genetics, 5(3), 274-278. https://doi.org/10.1038/ng1193-274

A mutation in CFTR produces different phenotypes depending on chromosomal background. / Kiesewetter, S.; Macek, M.; Davis, C.; Curristin, S. M.; Chu, C. S.; Graham, C.; Shrimpton, A. E.; Cashman, S. M.; Tsui, L. C.; Mickle, J.; Amos, J.; Highsmith, W Edward Jr.; Shuber, A.; Witt, D. R.; Crystal, R. G.; Cutting, G. R.

In: Nature Genetics, Vol. 5, No. 3, 1993, p. 274-278.

Research output: Contribution to journalArticle

Kiesewetter, S, Macek, M, Davis, C, Curristin, SM, Chu, CS, Graham, C, Shrimpton, AE, Cashman, SM, Tsui, LC, Mickle, J, Amos, J, Highsmith, WEJ, Shuber, A, Witt, DR, Crystal, RG & Cutting, GR 1993, 'A mutation in CFTR produces different phenotypes depending on chromosomal background', Nature Genetics, vol. 5, no. 3, pp. 274-278. https://doi.org/10.1038/ng1193-274
Kiesewetter S, Macek M, Davis C, Curristin SM, Chu CS, Graham C et al. A mutation in CFTR produces different phenotypes depending on chromosomal background. Nature Genetics. 1993;5(3):274-278. https://doi.org/10.1038/ng1193-274
Kiesewetter, S. ; Macek, M. ; Davis, C. ; Curristin, S. M. ; Chu, C. S. ; Graham, C. ; Shrimpton, A. E. ; Cashman, S. M. ; Tsui, L. C. ; Mickle, J. ; Amos, J. ; Highsmith, W Edward Jr. ; Shuber, A. ; Witt, D. R. ; Crystal, R. G. ; Cutting, G. R. / A mutation in CFTR produces different phenotypes depending on chromosomal background. In: Nature Genetics. 1993 ; Vol. 5, No. 3. pp. 274-278.
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