title: A population-based study of dystrophin mutations in Canada.
abstract: BACKGROUND
  We carried out a population-based study of dystrophin mutations in patients followed by members of the Canadian Paediatric Neuromuscular Group (CPNG) over a ten-year period.
  
  
  OBJECTIVE
  We aimed to describe the changes in diagnostic testing for dystrophinopathy and to determine the frequency of dystrophin mutations from 2000 to 2009.
  
  
  METHODS
  De-identified data containing the clinical phenotypes, diagnostic methods, and mutational reports from dystrophinopathy patients followed by CPNG centres from January 2000 to December 2009 were analyzed using descriptive statistics.
  
  
  RESULTS
  773 patients had a confirmed diagnosis of dystrophinopathy based on genetic testing (97%), muscle biopsy (2%), or family history (1%). 573 (74%) had complete deletion/duplication analysis of all 79 exons or whole gene sequencing, resulting in 366 (64%) deletions, 64 (11%) duplications, and 143 (25%) point mutations. The percentage of patients who were diagnosed using currently accepted genetic testing methods varied across Canada, with a mean of 63% (SD 23). 246 (43%) mutations involved exons 45 to 53. The top ten deletions (n=147, 26%) were exons 45-47, 45-48, 45, 45-50, 45-55, 51, 45-49, 45-52, 49-50, and 46-47. 169 (29%) mutations involved exons 2 to 20. The most common duplications (n=29, 5.1%) were exons 2, 2-7, 2-17, 3-7, 8-11, 10, 10-11, and 12.
  
  
  CONCLUSIONS
  This is the most comprehensive report of dystrophin mutations in Canada. Consensus guidelines regarding the diagnostic approach to dystrophinopathy will hopefully reduce the geographical variation in mutation detection rates in the coming decade.
authors.affiliation: Division of Neurology, Department of Paediatrics, University of Calgary, Alberta Children's Hospital, Calgary.
authors.forename: Jean K
authors.initials: JK
authors.lastname: Mah
authors.forename: Kathryn
authors.initials: K
authors.lastname: Selby
authors.forename: Craig
authors.initials: C
authors.lastname: Campbell
authors.forename: Amelie
authors.initials: A
authors.lastname: Nadeau
authors.forename: Mark
authors.initials: M
authors.lastname: Tarnopolsky
authors.forename: Anna
authors.initials: A
authors.lastname: McCormick
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Dooley
authors.forename: Hanna
authors.initials: H
authors.lastname: Kolski
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Skalsky
authors.forename: R Garth
authors.initials: RG
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Buckley
authors.forename: Peter N
authors.initials: PN
authors.lastname: Ray
authors.forename: Grace
authors.initials: G
authors.lastname: Yoon
mesh_terms: D002170:Canada; D018672:Community Health Planning; D016189:Dystrophin / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000145:classification / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D015995:Prevalence; D012189:Retrospective Studies; D013223:Statistics as Topic; D013997:Time Factors
chemical_list: D016189:Dystrophin