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 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.
KeywordsCystic fibrosis CFTR Mutation Japanese Asian
We are grateful to Drs. Yoichiro Abe and Masato Yasui (Keio University) for their useful help and discussions. We are also grateful to the Collaborative Research Resources, Keio University School of Medicine for equipment and technical supports. K.W.-N. is a Japan Society for the Promotion of Sciences (JSPS) Research Fellow. This work was supported by JSPS KAKENHI Grant Numbers 17J40033 (K.W.-N.), 25293049, 15K15035, 16H05122 (Y.S.), and 16K09392 (H.I.).
KW-N designed and performed the molecular biological and biochemical experiments and helped write the manuscript. Y-CY designed and performed the electro-physiological experiments and helped write the manuscript. MN designed the molecular biological experiments and T-CH designed the electro-physiological experiments. HI conceptualized the project and helped write the manuscript. YS conceptualized the project, designed the experiments, and helped write the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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