title: Clinical characterisation of Becker muscular dystrophy patients predicts favourable outcome in exon-skipping therapy.
abstract: OBJECTIVE
  Duchenne and Becker muscular dystrophy (DMD/BMD) are both caused by mutations in the DMD gene. Out-of-frame mutations in DMD lead to absence of the dystrophin protein, while in-frame BMD mutations cause production of internally deleted dystrophin. Clinically, patients with DMD loose ambulance around the age of 12, need ventilatory support at their late teens and die in their third or fourth decade due to pulmonary or cardiac failure. BMD has a more variable disease course. The disease course of patients with BMD with specific mutations could be very informative to predict the outcome of the exon-skipping therapy, aiming to restore the reading-frame in patients with DMD.
  
  
  METHODS
  Patients with BMD with a mutation equalling a DMD mutation after successful exon skipping were selected from the Dutch Dystrophinopathy Database. Information about disease course was gathered through a standardised questionnaire. Cardiac data were collected from medical correspondence and a previous study on cardiac function in BMD.
  
  
  RESULTS
  Forty-eight patients were included, representing 11 different mutations. Median age of patients was 43 years (range 6-67). Nine patients were wheelchair users (26-56 years). Dilated cardiomyopathy was present in 7/36 patients. Only one patient used ventilatory support. Three patients had died at the age of 45, 50 and 76 years, respectively.
  
  
  CONCLUSIONS
  This study provides mutation specific data on the course of disease in patients with BMD. It shows that the disease course of patients with BMD, with a mutation equalling a 'skipped' DMD mutation is relatively mild. This finding strongly supports the potential benefit of exon skipping in patients with DMD.
authors.affiliation: Department of Neurology, Leiden University Medical Center, , Leiden, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: van den Bergen
authors.forename: S M
authors.initials: SM
authors.lastname: Schade van Westrum
authors.forename: L
authors.initials: L
authors.lastname: Dekker
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: M
authors.initials: M
authors.lastname: de Visser
authors.forename: B H A
authors.initials: BH
authors.lastname: Wokke
authors.forename: C S
authors.initials: CS
authors.lastname: Straathof
authors.forename: M A
authors.initials: MA
authors.lastname: Hulsker
authors.forename: A
authors.initials: A
authors.lastname: Aartsma-Rus
authors.forename: J J
authors.initials: JJ
authors.lastname: Verschuuren
authors.forename: H B
authors.initials: HB
authors.lastname: Ginjaar
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000473:pathology; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D030541:Databases, Genetic; D004452:Echocardiography; D004522:Educational Status; D004562:Electrocardiography; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015316:Genetic Therapy / Q000379:methods*; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D009426:Netherlands / Q000453:epidemiology; D016019:Survival Analysis; D014910:Wheelchairs; D055815:Young Adult
keywords: DYSTROPHIN; MUSCLE DISEASE; MUSCULAR DYSTROPHY