title: Assessment of CFTR function in homozygous R117H-7T subjects.
abstract: BACKGROUND
  R117H is a frequent missense mutation included in most CFTR mutation panels. However knowledge about the residual function of R117H-CFTR channels in cystic fibrosis-affected organs, e.g. airways, intestines and sweat glands is presently lacking.
  
  
  METHODS
  We evaluated clinical CF symptoms and assessed CFTR function by sweat tests, nasal potential difference and intestinal current measurements in 2 homozygous R117H individuals (7T variant).
  
  
  RESULTS
  The CFTR activity in airways and intestine was within the normal range. However both individuals presented with a borderline sweat test and the male patient was infertile.
  
  
  CONCLUSIONS
  The lack of impact of the R117H mutation on chloride secretion in intestine and nose contrasts with the ~80% loss of CFTR activity reported in patch clamp studies. Apparently CFTR activity is not rate-limiting for chloride secretion in both tissues at levels >20% of normal, or compensatory factors may operate that are absent in heterologous host cells in vitro.
authors.affiliation: Department of Pulmonology, University Medical Centre Utrecht, GA Utrecht, The Netherlands. r.denooijer@umcutrecht.nl
authors.forename: R A
authors.initials: RA
authors.lastname: de Nooijer
authors.forename: J M
authors.initials: JM
authors.lastname: Nobel
authors.forename: H G M
authors.initials: HG
authors.lastname: Arets
authors.forename: A G
authors.initials: AG
authors.lastname: Bot
authors.forename: F Teding
authors.initials: FT
authors.lastname: van Berkhout
authors.forename: Y B
authors.initials: YB
authors.lastname: de Rijke
authors.forename: H R
authors.initials: HR
authors.lastname: de Jonge
authors.forename: I
authors.initials: I
authors.lastname: Bronsveld
mesh_terms: D000328:Adult; D001706:Biopsy; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006720:Homozygote; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000503:physiopathology; D007422:Intestines / Q000502:physiology; D008168:Lung / Q000502:physiology; D008297:Male; D020125:Mutation, Missense; D018408:Patch-Clamp Techniques; D013545:Sweat Glands / Q000502:physiology; D013546:Sweating / Q000502:physiology
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator