Two CFTR mutations within codon 970 differently impact on the chloride channel functionality
| العنوان: | Two CFTR mutations within codon 970 differently impact on the chloride channel functionality |
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| المؤلفون: | Ilaria Musante, Valeria Tomati, Giuseppe Castaldo, Luis J. V. Galietta, Emanuela Caci, Cesare Braggion, Felice Amato, Marika Comegna, Antonella Miriam Di Lullo, Elke De Wachter, Vito Terlizzi, Paolo Scudieri, Eef Vanderhelst, Francesca Manzoni, Sabrina Maietta |
| المساهمون: | Amato, Felice, Scudieri, Paolo, Musante, Ilaria, Tomati, Valeria, Caci, Emanuela, Comegna, Marika, Maietta, Sabrina, Manzoni, Francesca, Di Lullo, Antonella Miriam, De Wachter, Elke, Vanderhelst, Eef, Terlizzi, Vito, Braggion, Cesare, Castaldo, Giuseppe, Galietta, Luis J. V., Clinical sciences, Physiotherapy, Human Physiology and Anatomy, Pediatrics, Pneumology |
| المصدر: | Human mutation. 40(6) |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | chloride channel, Cystic Fibrosis, RNA Splicing, Mutant, Cystic Fibrosis Transmembrane Conductance Regulator, medicine.disease_cause, Transfection, Cystic fibrosis, 03 medical and health sciences, Genetic, Genetics, medicine, Missense mutation, Humans, Point Mutation, Genetics(clinical), CFTR, airway epithelium, cystic fibrosis, RNA splicing, Codon, HEK293 Cells, Phenotype, cystic fibrosi, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Mutation, biology, 030305 genetics & heredity, Potentiator, medicine.disease, Molecular biology, Cystic fibrosis transmembrane conductance regulator, Chloride channel, biology.protein |
| الوصف: | Pharmacological rescue of mutant cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis (CF) depends on the specific defect caused by different mutation classes. We asked whether a patient with the rare p.Gly970Asp (c.2909G>A) mutation could benefit from CFTR pharmacotherapy since a similar missense mutant p.Gly970Arg (c.2908G>C) was previously found to be sensitive to potentiators in vitro but not in vivo. By complementary DNA transfection, we found that both mutations are associated with defective CFTR function amenable to pharmacological treatment. However, analysis of messenger RNA (mRNA) from patient's cells revealed that c.2908G>C impairs RNA splicing whereas c.2909G>A does not perturb splicing and leads to the expected p.Gly970Asp mutation. In agreement with these results, nasal epithelial cells from the p.Gly970Asp patient showed significant improvement of CFTR function upon pharmacological treatment. Our results underline the importance of controlling the effect of CF mutation at the mRNA level to determine if the pharmacotherapy of CFTR basic defect is appropriate. |
| تدمد: | 1098-1004 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9b23ca4b9233446b29d4d800b1fafa7a https://pubmed.ncbi.nlm.nih.gov/30851139 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....9b23ca4b9233446b29d4d800b1fafa7a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10981004 |
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