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.

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Journal of Cystic Fibrosis
Erasmus MC: University Medical Center Rotterdam

de Nooijer, R. A., Nobel, J. M., Arets, H., Bot, A., van Berkhout, T., de Rijke, Y., … Bronsveld, I. (2011). Assessment of CFTR function in homozygous R117H-7T subjects. Journal of Cystic Fibrosis, 10(5), 326–332. doi:10.1016/j.jcf.2011.03.009