Phenotypic and molecular characteristics of CF patients carrying the I1234V mutation

• Published in: Respiratory medicine 2020-08, Vol.170, p.106027-106027, Article 106027
• Main Authors: El Bar Aluma, Bat, Sarouk, Ifat, Senderowitz, Hanoch, Cohen-Cymberknoh, Malena, Khazanov, Netaly, Dagan, Adi, Bezalel, Yael, Ashkenazi, Moshe, Keler, Shlomit, Efrati, Ori
• Format: Article
• Language: English
• Subjects: Chloride; Computer applications; Computer simulation; Construction; Cystic fibrosis; Data collection; Diabetes; FDA approval; I1234V CF mutation; Lipids; Liver diseases; Mathematical models; Medical records; Modulator therapy; Mutation; Patients; Proteins; Structural CFTR models; Structural models
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2020.106027

The Mutation I1234V is a CF causing mutation; however the mechanisms leading to loss of function are not fully understood. In this study, we aimed to characterize phenotypically individuals with the I1234V variant, and to gain a structural point of view of the mutant CFTR using computational studies. We conducted a retrospective descriptive study, reviewing the clinical records of 9 Israeli patients. The study was designed to include patients either homozygous or compound heterozygous for the I1234V mutation. For a comparison we analyzed clinical data of 12 patients homozygous for the F508del mutation. Computer models were constructed for I1234V, 1234-1239del and wild type CFTR. Mean FEV1 was 73.8 ± 21% predicted with an average annual rate of decline of 1%. When compared to patients homozygous for F508del the mean annual values of FEV1% predicted during the 6 years of data collection ranged from 51 to 58 ± 22–30 in the F508del group versus 76–82 ± 14–19 in the I1234V group (p