title: Non-Ambulant Duchenne Patients Theoretically Treatable by Exon 53 Skipping have Severe Phenotype.
abstract: BACKGROUND
  Exon skipping therapy is an emerging approach in Duchenne Muscular Dystrophy (DMD). Antisense oligonucleotides that induce skipping of exon 51, 44, 45, or 53 are currently being evaluated in clinical trials. These trials were designed on the basis of data available in general DMD population.
  
  
  OBJECTIVE
  Our objective was to compare the clinical and functional statuses of non-ambulant DMD patients theoretically treatable by exon 53 skipping and of DMD patients with other mutations.
  
  
  METHODS
  We first compared fifteen non-ambulant DMD patients carrying deletions theoretically treatable by exon 53 skipping (DMD-53) with fifteen closely age-matched DMD patients with mutations not treatable by exon 53 skipping (DMD-all-non-53) then with fifteen DMD patients carrying deletions not treatable by exon 53 skipping (DMD-del-non-53).
  
  
  RESULTS
  We found that DMD-53 patients had a lower left ventricular ejection fraction, more contractures and they tend to have weaker grips and pinch strengths than other DMD patients. DMD-53 patients lost ambulation significantly younger than other DMD patients. This result was confirmed by comparing ages at loss of ambulation in all non-ambulant DMD patients of the DMD cohort identified in a molecular diagnostic lab.
  
  
  CONCLUSIONS
  These prospective and retrospective data demonstrate that DMD-53 patients have clinically more severe phenotypes than other DMD patients.
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Servais
authors.affiliation: Généthon, Evry, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Montus
authors.affiliation: Généthon, Evry, France.|Atlantic Gene Therapies, INSERM UMR, Nantes, France.
authors.forename: Caroline Le
authors.initials: CL
authors.lastname: Guiner
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.|Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, APHP, Paris, France.
authors.forename: Rabah
authors.initials: R
authors.lastname: Ben Yaou
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Annoussamy
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Moraux
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Hogrel
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
authors.forename: Andreea M
authors.initials: AM
authors.lastname: Seferian
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Zehrouni
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Le Moing
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gidaro
authors.affiliation: Service de Pédiatrie, Centre Hospitalier Universitaire (CHU), Rouen, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vanhulle
authors.affiliation: Service de Pédiatrie, Centre Hospitalier Universitaire (CHU), Strasbourg, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Laugel
authors.affiliation: Pediatric Neurology Clinic, Alexandru Obregia Hospital, Bucharest, Romania.
authors.forename: Nina
authors.initials: N
authors.lastname: Butoianu
authors.affiliation: Service de Neuropédiatrie, Centre hospitalier régional universitaire et faculté de médecine, Lille, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Cuisset
authors.affiliation: Service de Pédiatrie A, Hôpital Américain, CHU de Reims, Reims, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sabouraud
authors.affiliation: Service de Neurologie Pédiatrique, Hôpital des Enfants, Toulouse, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Cances
authors.affiliation: Department of pediatric neurology, University Children's Hospital, Zurich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Klein
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.|Laboratoire de biochimie et génétique moléculaire, Hôpital Cochin, APHP, Paris, France.
authors.forename: France
authors.initials: F
authors.lastname: Leturcq
authors.affiliation: Généthon, Evry, France.|Atlantic Gene Therapies, INSERM UMR, Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moullier
authors.affiliation: Institut de Myologie, Groupe hospitalier La Pitié Salpêtrière, AP-HP, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
keywords: Duchenne muscular dystrophy; exon skipping; outcome measures; phenotype-genotype correlation