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Translating the genetics of cystic fibrosis to personalized medicine

  • Harriet Corvol
    Affiliations
    INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France

    Sorbonne Universités, UPMC University Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France

    Pneumologie pédiatrique, APHP, Hôpital Trousseau, Paris, France
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  • Kristin E. Thompson
    Affiliations
    INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France

    Sorbonne Universités, UPMC University Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France
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  • Olivier Tabary
    Affiliations
    INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France

    Sorbonne Universités, UPMC University Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France
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  • Philippe le Rouzic
    Affiliations
    INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France

    Sorbonne Universités, UPMC University Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France
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  • Loïc Guillot
    Correspondence
    Reprint requests: Loïc Guillot, INSERM, UMR_S 938, CDR Saint Antoine, Inserm, Bât. Kourilsky 2ème Étage, 34 Rue Crozatier, 75012 Paris, France
    Affiliations
    INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France

    Sorbonne Universités, UPMC University Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France
    Search for articles by this author
Published:April 15, 2015DOI:https://doi.org/10.1016/j.trsl.2015.04.008
      Cystic fibrosis (CF) is the most common life-threatening recessive genetic disease in the Caucasian population. This multiorgan disease is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein, a chloride channel recognized as regulating several apical ion channels. The gene mutations result either in the lack of the protein at the apical surface or in an improperly functioning protein. Morbidity and mortality because of the mutation of CFTR are mainly attributable to lung disease resulting from chronic infection and inflammation. Since its discovery as the causative gene in 1989, much progress has been achieved not only in clinical genetics but also in basic science studies. Recently, combinations of these efforts have been successfully translated into development and availability for patients of new therapies targeting specific CFTR mutations to correct the CFTR at the protein level. Current technologies such as next gene sequencing and novel genomic editing tools may offer new strategies to identify new CFTR variants and modifier genes, and to correct CFTR to pursue personalized medicine, which is already developed in some patient subsets. Personalized medicine or P4 medicine (“personalized,” “predictive,” “preventive,” and “participatory”) is currently booming for CF. The various current and future challenges of personalized medicine as they apply to the issues faced in CF are discussed in this review.

      Abbreviations:

      AAV (Adeno associated virus), ABC (ATP-binding cassette), ACMG (American College Medical Genetics), AH (Ancestral Haplotype), ASL (airway surface liquid), ATP (Adenosine triphosphate), cas (CRISPR associated), CF (Cystic fibrosis), CFTR (Cystic Fibrosis Transmembrane conductance Regulator), CFTR2 (Clinical and Functional Translation of CFTR), CRISPR (clustered regulatory interspaced short palindromic repeat), CYP3A (cytochrome P450 family 3, subfamily A), DDI (drug-drug interaction), EMA (European Medical Agency), ER (Endoplasmic reticulum), FDA (Food and Drug Administration), FEV1 (Forced Expiratory Volume in 1s), G (Golgi), gRNA (guide RNA), GWAS (Genome Wide Association Studies), HGVS (Human Genome Variation Society), HSPA1B (Heat Shock Protein A1B), iPSC (induced pluripotent stem cell), MBL2 (Mannose Binding Lectin 2), MHC (Major Histocompatibility Complex), NBD (nucleotide-binding domain), NGS (Next Gene Sequencing), P-gp (P-glycoprotein), PTC (premature termination codon), R (regulatory domain), RAGE (Receptor for Advanced Glycation Endproducts), TALEN (transcription activator-like effector nuclease), TGFB1 (Transforming Growth Factor Beta 1), TLR (Toll Like Receptor), TMD (transmembrane domain), TNF (Tumor Necrosis Factor), ZFN (zinc finger nuclease)
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