1. Assessment of CFTR function in homozygous R117H-7T subjects.
- Author
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de Nooijer RA, Nobel JM, Arets HG, Bot AG, van Berkhout FT, de Rijke YB, de Jonge HR, and Bronsveld I
- Subjects
- Adult, Biopsy, Chlorides metabolism, Female, Homozygote, Humans, Infertility, Male genetics, Infertility, Male physiopathology, Intestines physiology, Lung physiology, Male, Patch-Clamp Techniques, Sweat Glands physiology, Sweating physiology, Cystic Fibrosis genetics, Cystic Fibrosis physiopathology, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Mutation, Missense
- 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., (Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)
- Published
- 2011
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