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.
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.
Authors: Felix Ratjen; Scott C Bell; Steven M Rowe; Christopher H Goss; Alexandra L Quittner; Andrew Bush Journal: Nat Rev Dis Primers Date: 2015-05-14 Impact factor: 52.329
Authors: Kavisha Arora; Yunjie Huang; Kyushik Mun; Sunitha Yarlagadda; Nambirajan Sundaram; Marco M Kessler; Gerhard Hannig; Caroline B Kurtz; Inmaculada Silos-Santiago; Michael Helmrath; Joseph J Palermo; John P Clancy; Kris A Steinbrecher; Anjaparavanda P Naren Journal: JCI Insight Date: 2017-10-05
Authors: Jessica E Char; Marlene H Wolfe; Hyung-Ju Cho; Il-Ho Park; Jin Hyeok Jeong; Eric Frisbee; Colleen Dunn; Zoe Davies; Carlos Milla; Richard B Moss; Ewart A C Thomas; Jeffrey J Wine Journal: PLoS One Date: 2014-02-10 Impact factor: 3.240
Authors: Michal Shteinberg; Damian G Downey; Diane Beattie; John McCaughan; Alastair Reid; Nili Stein; J Stuart Elborn Journal: ERJ Open Res Date: 2017-03-31
Authors: Jessica E Char; Colleen Dunn; Zoe Davies; Carlos Milla; Richard B Moss; Jeffrey J Wine Journal: PLoS One Date: 2017-04-18 Impact factor: 3.240
Authors: Jeffrey KiHyun Park; Anura Shrivastava; Chengkang Zhang; Brian A Pollok; Walter E Finkbeiner; Elizabeth R Gibb; Ngoc P Ly; Beate Illek Journal: Front Pediatr Date: 2020-09-04 Impact factor: 3.418
Authors: Keith Nykamp; Rebecca Truty; Darlene Riethmaier; Julia Wilkinson; Sara L Bristow; Sienna Aguilar; Dana Neitzel; Nicole Faulkner; Swaroop Aradhya Journal: Hum Mutat Date: 2021-07-10 Impact factor: 4.700