Characterization of Δ(G970-T1122)-CFTR, the most frequent CFTR mutant identified in Japanese cystic fibrosis patients

A massive deletion over three exons 16-17b in the CFTR gene was identified in Japanese CF patients with the highest frequency (about 70% of Japanese CF patients definitely diagnosed). This pathogenic mutation results in a deletion of 153 amino acids from glycine at position 970 (G970) to threonine a...

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Published inThe journal of physiological sciences Vol. 69; no. 1; pp. 103 - 112
Main Authors Wakabayashi-Nakao, Kanako, Yu, Yingchun, Nakakuki, Miyuki, Hwang, Tzyh-Chang, Ishiguro, Hiroshi, Sohma, Yoshiro
Format Journal Article
LanguageEnglish
Published Japan BioMed Central 01.01.2019
Springer Japan
Subjects
Animals
CHO Cells
Clonal deletion
Cricetulus
Cystic fibrosis
Cystic Fibrosis - genetics
Cystic fibrosis transmembrane conductance regulator
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Exons
Female
Gene deletion
Glycine
Humans
Japan
Male
Mutation
Original Paper
Patch-Clamp Techniques
Sequence Deletion
Threonine
Japan
Cystic fibrosis
Mutation
Asian
Japanese
CFTR
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Summary:A massive deletion over three exons 16-17b in the CFTR gene was identified in Japanese CF patients with the highest frequency (about 70% of Japanese CF patients definitely diagnosed). This pathogenic mutation results in a deletion of 153 amino acids from glycine at position 970 (G970) to threonine at 1122 (T1122) in the CFTR protein without a frameshift. We name it Δ(G970-T1122)-CFTR. In the present study, we characterized the Δ(G970-T1122)-CFTR expressed in CHO cells using immunoblots and a super resolution microscopy. Δ(G970-T1122)-CFTR proteins were synthesized and core-glycosylated but not complex-glycosylated. This observation suggests that the Δ(G970-T1122) mutation can be categorized into the class II mutation like ΔF508. However, VX-809 a CFTR corrector that can help maturation of ΔF508, had no effect on Δ(G970-T1122). Interestingly C-terminal FLAG tag seems to partially rescue the trafficking defect of Δ(G970-T1122)-CFTR; however the rescued Δ(G970-T1122)-CFTR proteins do not assume channel function. Japanese, and perhaps people in other Asian nations, carry a class II mutation Δ(G970-T1122) with a higher frequency than previously appreciated. Further study of the Δ(G970-T1122)-CFTR is essential for understanding CF and CFTR-related diseases particularly in Asian countries.
ISSN:1880-6546
1880-6562
DOI:10.1007/s12576-018-0626-4