title: Function, pharmacological correction and maturation of new Indian CFTR gene mutations.
abstract: BACKGROUND
  Cystic fibrosis (CF) is rare in India. Most CF mutations identified are not yet functionally characterized. Hence, genetic counseling and adoption of therapeutic approach are particularly difficult. Our aim was to study the function and maturation of a spectrum of eleven Indian CFTR mutations from classical CF and infertile male patients with CBAVD.
  
  
  METHODS
  We used Western blot, pharmacology and iodide efflux to study CFTR maturation and chloride transport in BHK cells expressing pEGFP-CFTR constructs for L69H, F87I, S118P, G126S, H139Q, F157C, F494L, E543A, S549N, Y852F and D1270E.
  
  
  RESULTS
  Among these CFTR mutants, only L69H is not processed as a c-band and not functional at 37°C. However, the functions of L69H and S549N and the maturation of L69H are corrected at 27°C and by the investigational drug VX809.
  
  
  CONCLUSIONS
  These data should help in developing counseling and therapeutic approaches in India. We identified L69H as a novel class II CF mutation.
authors.affiliation: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers, CNRS, Poitiers, France; Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh160012, India.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Sharma
authors.affiliation: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers, CNRS, Poitiers, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Jollivet Souchet
authors.affiliation: Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie (IMPMC), Sorbonne Universités - UPMC Université Paris 06, UMR CNRS 7590, Muséum National d'Histoire Naturelle, IRD UMR 206, 4 Place Jussieu, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Callebaut
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh160012, India. Electronic address: fateh1977@yahoo.com.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers, CNRS, Poitiers, France. Electronic address: frederic.becq@univ-poitiers.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Becq
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D003550:Cystic Fibrosis / Q000453:epidemiology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007194:India; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D052801:Male Urogenital Diseases / Q000235:genetics*; D020125:Mutation, Missense / Q000187:drug effects; D035583:Rare Diseases; D012494:Sampling Studies; D012741:Sexual Maturation / Q000235:genetics; D014649:Vas Deferens / Q000002:abnormalities*
chemical_list: D000631:Aminopyridines; D052117:Benzodioxoles; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C569105:lumacaftor
keywords: India; L69H-CFTR; Low temperature; Missense CF mutations; S549N-CFTR; VX809