title: c.3623G > A mutation encodes a CFTR protein with impaired channel function.
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.
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, 50 North Dunlap Street, Memphis, TN, 38103, USA.|University of Tennessee Cystic Fibrosis Care and Research Center, Le Bonheur Children's Hospital-Methodist University Hospital, Memphis, TN, 38103, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, 50 North Dunlap Street, Memphis, TN, 38103, USA.|University of Tennessee Cystic Fibrosis Care and Research Center, Le Bonheur Children's Hospital-Methodist University Hospital, Memphis, TN, 38103, USA.
authors.forename: Jaspal S
authors.initials: JS
authors.lastname: Hothi
authors.affiliation: Department of Bioscience Research, University of Tennessee Health Science Center, 875 Union Avenue, Memphis, TN, 38163, USA.
authors.forename: Yanhui H
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, 50 North Dunlap Street, Memphis, TN, 38103, USA.|University of Tennessee Cystic Fibrosis Care and Research Center, Le Bonheur Children's Hospital-Methodist University Hospital, Memphis, TN, 38103, USA.
authors.forename: Saumini
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, 50 North Dunlap Street, Memphis, TN, 38103, USA.|University of Tennessee Cystic Fibrosis Care and Research Center, Le Bonheur Children's Hospital-Methodist University Hospital, Memphis, TN, 38103, USA.
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Stokes
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, 50 North Dunlap Street, Memphis, TN, 38103, USA. wzhang16@uthsc.edu.|Department of Physiology, University of Tennessee Health Science Center, 50 North Dunlap Street, Room 309R, Memphis, TN, 38103, USA. wzhang16@uthsc.edu.|University of Tennessee Cystic Fibrosis Care and Research Center, Le Bonheur Children's Hospital-Methodist University Hospital, Memphis, TN, 38103, USA. wzhang16@uthsc.edu.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Zhang
mesh_terms: D001741:Black or African American / Q000235:genetics*; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D006801:Humans; D007223:Infant; D015640:Ion Channel Gating / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator