Identification of mutations in exons 1 through 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene

Julian Zielenski*, Dominique Bozon, Bat sheva Kerem, Danuta Markiewicz, Peter Durie, Johanna M. Rommens, Lap Chee Tsui

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

171 Scopus citations


Five different mutations have been identified in the gene causing cystic fibrosis (CF) through sequencing regions encompassing exons 1-8, including the 5′ untranslated leader. Two of these apparent mutations are missense mutations, one in exon 3 (Gly to Glu at position 85; G85E) and another in exon 5 (Gly to Arg at 178; G178R), both causing significant changes in the corresponding amino acids in the encoded protein-cystic fibrosis transmembrane conductance regulator (CFTR). Two others affect the highly conserved RNA splice junction flanking the 3′ end of exons 4 and 5 (621 + 1G → T, 711 + 1G → T), resulting in a probable splicing defect. The last mutation is a single-basepair deletion in exon 4, causing a frameshift. These five mutations account for the 9 of 31 non-ΔF508 CF chromosomes in our Canadian CF family collection and they are not found in any of the normal chromosomes. Three of the mutations, 621 + 1G → T, 711 + 1G → T, and G85E, are found in the French-Canadian population, with 621 + 1G → T being the most abundant ( 5 7). There are two other sequence variations in the CFTR gene; one of them (129G → C) is located 4 nucleotides upstream of the proposed translation initiation codon and, although present only on CF chromosomes, it is not clear whether it is a disease-causing mutation; the other (R75Q) is most likely a sequence variation within the coding region.

Original languageAmerican English
Pages (from-to)229-235
Number of pages7
Issue number1
StatePublished - May 1991
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Dara Kennedy for her expert technical assistance, and Mary Fujiwara and Richard Rozmahel for helpful discussions. The availability of the CF patient database at the Hospital for Sick Children in Toronto is also gratefully acknowledged. The research was supported by grants from the National Institutes of Health (U.S.A.) (DK-34944-53, the Cystic Fibrosis Foundation (U.S.A.), and the Canadian Cystic Fibrosis Foundation. L.-C.T. is a recipient of the Scientist Award from the Medical Research Council of Canada.


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