title: CMTX1 patients' cells present genomic instability corrected by CamKII inhibitors.
abstract: BACKGROUND
  We previously described that fibroblasts from animal models of CMTX1 present genomic instability and poor connexon activity. In vivo, these transgenic mice present motor deficits. This phenotype could be significantly reverted by treatment with (CamKII) inhibitors. The objective of this study is to translate our findings to patients.
  
  
  METHODS
  We cultured fibroblasts from skin biopsies of CMTX1 patients and analyzed cells for genomic instabilty, connexon activity, and potential correction by CamKII inhibitors.
  
  
  RESULTS
  The phenotypic analysis of these cells confirmed strong similarities between the GJB1 transgenic mouse cell lines and CMTX1 patient fibroblast cell lines. Both present mitotic anomalies, centrosome overduplication, and connexon activity deficit. This phenotype is corrected by CamKII inhibitors.
  
  
  CONCLUSIONS
  Our data demonstrate that fibroblasts from CMTX1 patients present a phenotype similar to transgenic lines that can be corrected by CamKII inhibitors. This presents a track to develop therapeutic strategies for CMTX1 treatment.
authors.affiliation: NORT. UMR INSERM 1062, INRA 1260, Aix Marseille Université, Campus Santé La Timone, 27 boulevard Jean Moulin, Marseille, 13385 Cedex 53, France. saleh.mones@univ-amu.fr.
authors.forename: Saleh
authors.initials: S
authors.lastname: Mones
authors.affiliation: Department of Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Muenster, Germany. burkhard.gess@gmail.com.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Gess
authors.affiliation: NORT. UMR INSERM 1062, INRA 1260, Aix Marseille Université, Campus Santé La Timone, 27 boulevard Jean Moulin, Marseille, 13385 Cedex 53, France. benoit.bordignon@inserm.fr.
authors.forename: Benoit
authors.initials: B
authors.lastname: Bordignon
authors.affiliation: Service de Microscopie Electronique, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, Marseille, 13385 Cedex 53, France. alexandre.altie@univ-amu.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Altié
authors.affiliation: Department of Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Muenster, Germany. Peter.Young@ukmuenster.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Young
authors.affiliation: Laboratoire d'Innovation thérapeutique, UMR7200, CNRS, Université de Strasbourg, Faculté de Pharmacie, 74, route du rhin, Illkirch Graffenstaden, 67400, France. Frederic.bihel@unistra.fr.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bihel
authors.affiliation: Department of Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Muenster, Germany. marc.fraterno@univ-amu.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Fraterno
authors.affiliation: NORT. UMR INSERM 1062, INRA 1260, Aix Marseille Université, Campus Santé La Timone, 27 boulevard Jean Moulin, Marseille, 13385 Cedex 53, France. franck.peiretti@univ-amu.fr.
authors.forename: Franck
authors.initials: F
authors.lastname: Peiretti
authors.affiliation: NORT. UMR INSERM 1062, INRA 1260, Aix Marseille Université, Campus Santé La Timone, 27 boulevard Jean Moulin, Marseille, 13385 Cedex 53, France. michel.fontes@univ-amu.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Fontes
authors.affiliation: NORT. UMR INSERM 1062, INRA 1260, Aix Marseille Université, Campus Santé La Timone, 27 boulevard Jean Moulin, Marseille, 13385 Cedex 53, France. saleh.mones@univ-amu.fr.
authors.forename: Mones
authors.initials: M
authors.lastname: Saleh
authors.affiliation: Department of Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Muenster, Germany. burkhard.gess@gmail.com.|Department of Neurology, Aachen RWTH University Clinic, Aachen, Germany. burkhard.gess@gmail.com.
authors.forename: Gess
authors.initials: G
authors.lastname: Burkhardt
authors.affiliation: NORT. UMR INSERM 1062, INRA 1260, Aix Marseille Université, Campus Santé La Timone, 27 boulevard Jean Moulin, Marseille, 13385 Cedex 53, France. benoit.bordignon@inserm.fr.
authors.forename: Bordignon
authors.initials: B
authors.lastname: Benoit
authors.affiliation: Service de Microscopie Electronique, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, Marseille, 13385 Cedex 53, France. alexandre.altie@univ-amu.fr.
authors.forename: Altié
authors.initials: A
authors.lastname: Alexandre
authors.affiliation: Department of Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Muenster, Germany. Peter.Young@ukmuenster.de.
authors.forename: Young
authors.initials: Y
authors.lastname: Peter
authors.affiliation: Laboratoire d'Innovation thérapeutique, UMR7200, CNRS, Université de Strasbourg, Faculté de Pharmacie, 74, route du rhin, Illkirch Graffenstaden, 67400, France. Frederic.bihel@unistra.fr.
authors.forename: Bihel
authors.initials: B
authors.lastname: Frederic
authors.affiliation: Department of Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Muenster, Germany. marc.fraterno@univ-amu.fr.
authors.forename: Fraterno
authors.initials: F
authors.lastname: Marc
authors.affiliation: NORT. UMR INSERM 1062, INRA 1260, Aix Marseille Université, Campus Santé La Timone, 27 boulevard Jean Moulin, Marseille, 13385 Cedex 53, France. franck.peiretti@univ-amu.fr.
authors.forename: Peiretti
authors.initials: P
authors.lastname: Franck
authors.affiliation: NORT. UMR INSERM 1062, INRA 1260, Aix Marseille Université, Campus Santé La Timone, 27 boulevard Jean Moulin, Marseille, 13385 Cedex 53, France. michel.fontes@univ-amu.fr.
authors.forename: Fontes
authors.initials: F
authors.lastname: Michel
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors*; D002460:Cell Line; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D042822:Genomic Instability / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2