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Two CFTR mutations within codon 970 differently impact on the chloride channel functionality.
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.
Afiliação
  • Amato F; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, CEINGE - Biotecnologie Avanzate, Naples, Italy.
  • Scudieri P; Cell Biology and Disease Mechanisms Program, Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
  • Musante I; Cell Biology and Disease Mechanisms Program, Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
  • Tomati V; UOC Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
  • Caci E; UOC Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
  • Comegna M; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, CEINGE - Biotecnologie Avanzate, Naples, Italy.
  • Maietta S; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, CEINGE - Biotecnologie Avanzate, Naples, Italy.
  • Manzoni F; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, CEINGE - Biotecnologie Avanzate, Naples, Italy.
  • Di Lullo AM; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, CEINGE - Biotecnologie Avanzate, Naples, Italy.
  • De Wachter E; CF Centre, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
  • Vanderhelst E; CF Centre, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
  • Terlizzi V; Centro Regionale Toscano Fibrosi Cistica, Azienda Ospedaliero-Universitaria Meyer, Firenze, Italy.
  • Braggion C; Centro Regionale Toscano Fibrosi Cistica, Azienda Ospedaliero-Universitaria Meyer, Firenze, Italy.
  • Castaldo G; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, CEINGE - Biotecnologie Avanzate, Naples, Italy.
  • Galietta LJV; Cell Biology and Disease Mechanisms Program, Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
Hum Mutat ; 40(6): 742-748, 2019 06.
Article em En | MEDLINE | ID: mdl-30851139
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Mutação Puntual / Regulador de Condutância Transmembrana em Fibrose Cística / Fibrose Cística Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Mutação Puntual / Regulador de Condutância Transmembrana em Fibrose Cística / Fibrose Cística Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article