Abstract
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. 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. 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. 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.
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Citations
Jan 20, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Misak HarutyunyanAnjaparavanda P Naren
Mar 4, 2020·Personalized Medicine·Fouzia RadouaniNicola Mulder
Apr 16, 2019·FEBS Open Bio·Kaisheng LiuYong Dai
Nov 11, 2020·FEBS Letters·Narakorn Khunweeraphong, Karl Kuchler
Feb 12, 2021·Life·Xiaoying ZhangWeiqiang Zhang