Assessment of CFTR function in homozygous R117H-7T subjects

作者：de Nooijer R A^*; Nobel J M; Arets H G M; Bot A G; van Berkhout F Teding; de Rijke Y B; de Jonge H R; Bronsveld I

来源：Journal of Cystic Fibrosis, 2011, 10(5): 326-332.

DOI：10.1016/j.jcf.2011.03.009

• Cystic fibrosis
• R117H
• NPD
• ICM
• CFTR

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 similar to 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.

• 出版日期2011-9