Translating the genetics of cystic fibrosis to personalized medicine.
Harriet Corvol, Kristin E Thompson, Olivier Tabary, Philippe le Rouzic, Loïc Guillot
Author Information
Harriet Corvol: 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.
Kristin E Thompson: INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France; Sorbonne Universités, UPMC University Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France.
Olivier Tabary: INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France; Sorbonne Universités, UPMC University Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France.
Philippe le Rouzic: INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France; Sorbonne Universités, UPMC University Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France.
Loïc Guillot: INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France; Sorbonne Universités, UPMC University Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France. Electronic address: loic.guillot@inserm.fr.
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.
