C.3623G > A mutation encodes a CFTR protein with impaired channel function. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Zhang, Xiaoying; Hothi, Jaspal; Zhang, Yanhui; Srinivasan, Saumini; Stokes, Dennis; Zhang, Weiqiang
• Is Part Of: Respiratory research. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 6
• Publication Date: 2016-12
• Subjects: Cystic fibrosis (CF) -- CFTR -- CFTR mutations -- CFTR modulators -- VX-809; Respiratory organs -- Diseases -- Periodicals; 616.2005
• DOI: 10.1186/s12931-016-0326-7
• Languages: English
• ISSNs: 1465-993X

Abstract

Abstract Background The aims of this study were to characterize clinical features of a pediatric African-American cystic fibrosis (CF) patient heterozygous for F508del and a novel c.3623G > A mutation, and to identify the molecular defect(s) associated with c.3623G > A mutation. Methods The medical record of this patient was analyzed retrospectively. Western blotting and iodide efflux assay were used to study mutant CFTR protein expression level, maturation status, channel function, and the effects of CFTR modulation on these characteristics. Results The encoding protein of c.3623G > A mutation, G1208D-CFTR, has a moderate processing defect and exhibits impaired channel function, which were partially rescued by using VX-809 or exposed to low temperature (28 °C). The patient has mild CF disease manifestations. Conclusions Our biochemical findings correlate with the clinical phenotype and suggest that c.3623G > A is a CF-causing mutation. The study helps expand our knowledge of rare CFTR mutations in a minority population and may have important clinical implications for personalized therapeutic intervention.