[HTML][HTML] Assessment of CFTR function in homozygous R117H-7T subjects

RA De Nooijer, JM Nobel, HGM Arets, AG Bot… - Journal of Cystic …, 2011 - Elsevier
RA De Nooijer, JM Nobel, HGM Arets, AG Bot, FT van Berkhout, YB de Rijke, HR de Jonge…
Journal of Cystic Fibrosis, 2011Elsevier
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, eg 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 …
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.
Elsevier