Assessment of CFTR function in homozygous R117H-7T subjects

被引：26

作者：

de Nooijer, R. A. ^{[1
]}

Nobel, J. M. ^{[1
]}

Arets, H. G. M. ^{[2
]}

Bot, A. G. ^{[1
]}

van Berkhout, F. Teding ^{[1
]}

de Rijke, Y. B. ^{[3
]}

de Jonge, H. R. ^{[1
,4
]}

Bronsveld, I. ^{[1
]}

机构：

[1] Univ Med Ctr Utrecht, Dept Pulmonol, NL-3508 GA Utrecht, Netherlands

[2] Wilhelmina Childrens Hosp, Univ Med Ctr Utrecht, Dept Paediat Pulmonol, NL-3508 GA Utrecht, Netherlands

[3] Erasmus MC Sophia, Dept Clin Chem, NL-3000 CA Rotterdam, Netherlands

[4] Erasmus MC, Dept Biochem, NL-3000 CA Rotterdam, Netherlands

来源：

JOURNAL OF CYSTIC FIBROSIS | 2011年 / 10卷 / 05期

关键词：

Cystic fibrosis; R117H; NPD; ICM; CFTR; RESIDUAL CHLORIDE SECRETION; CYSTIC-FIBROSIS; DISEASE MUTATION; ION-TRANSPORT; LUNG-DISEASE; CONDUCTANCE; DIAGNOSIS; GUIDELINES; EPITHELIA; PHENOTYPE;

D O I：

10.1016/j.jcf.2011.03.009

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

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. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

引用

页码：326 / 332

页数：7

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