TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Haq, Iram J.
A1  - Althaus, Mike
A1  - Gardner, Aaron Ions
A1  - Yeoh, Hui Ying
A1  - Joshi, Urjita
A1  - Saint-Criq, Vinciane
A1  - Verdon, Bernard
A1  - Townshend, Jennifer
A1  - O'Brien, Christopher
A1  - Ben-Hamida, Mahfud
A1  - Thomas, Matthew
A1  - Bourke, Stephen
A1  - van der Sluijs, Peter
A1  - Braakman, Ineke
A1  - Ward, Chris
A1  - Gray, Michael A.
A1  - Brodlie, Malcolm
T1  - Clinical and molecular characterization of the R751L-CFTR mutation
JF  - American Journal of Physiology: Lung Cellular and Molecular Physiology
N2  - Cysticfibrosis (CF) arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in progressiveand life-limiting respiratory disease. R751L is a rare CFTR mutation that is poorly characterized. Our aims were to describe theclinical and molecular phenotypes associated with R751L. Relevant clinical data were collected from three heterozygote individu-als harboring R751L (2 patients with G551D/R751L and 1 with F508del/R751L). Assessment of R751L-CFTR function was made inprimary human bronchial epithelial cultures (HBEs) andXenopusoocytes. Molecular properties of R751L-CFTR were investigatedin the presence of known CFTR modulators. Although sweat chloride was elevated in all three patients, the clinical phenotypeassociated with R751L was mild. Chloride secretion in F508del/R751L HBEs was reduced compared with non-CF HBEs and asso-ciated with a reduction in sodium absorption by the epithelial  sodium  channel  (ENaC). However, R751L-CFTR function inXenopusoocytes, together with folding and cell surface transport of R751L-CFTR, was not different from wild-type CFTR. Overall,R751L-CFTR was associated with reduced sodium chloride absorption but had functional properties similar to wild-type CFTR.This is thefirst report of R751L-CFTR that combines clinical phenotype with characterization of functional and biological proper-ties of the mutant channel. Our work will build upon existing knowledge of mutations within this region of CFTR and, importantly,inform approaches for clinical management. Elevated sweat chloride and reduced chloride secretion in HBEs may be due to al-ternative non-CFTR factors, which require further investigation.
KW  - CFTR mutations
KW  - cysticfibrosis
KW  - primary airway epithelial cells
KW  - R751L
Y1  - 2021
UN  - https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-52631
SN  - 1040-0605
SS  - 1040-0605
U6  - https://doi.org/10.1152/ajplung.00137.2020
DO  - https://doi.org/10.1152/ajplung.00137.2020
PM  - 33296276
VL  - 320
IS  - 2
SP  - L288
EP  - L300
PB  - American Physiological Society
CY  - Bethesda, MD, USA
ER  -