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Measurement of the clinical utility of a combined mutation detection protocol in carriers of Duchenne and Becker muscular dystrophy
  1. Peter J Taylor1,
  2. Sarah Maroulis1,*,
  3. Glenda L Mullan1,*,
  4. Robyn L Pedersen2,
  5. Aurora Baumli1,
  6. George Elakis1,
  7. Sara Piras1,
  8. Corrina Walsh1,
  9. Benito Prósper-Gutiérrez1,
  10. Fernando De La Puente-Alonso1,
  11. Christopher G Bell1,
  12. David R Mowat2,
  13. Heather M Johnston2,
  14. Michael F Buckley1
  1. 1Molecular and Cytogenetics Unit, Department of Haematology and Genetics, South Eastern Area Laboratory Services, Prince of Wales Hospital, Randwick, Sydney, Australia
  2. 2Neuromuscular Clinic, Sydney Children’s Hospital, Randwick, Sydney, Australia
  1. Correspondence to:
 Dr M F Buckley
 Director of Laboratory Genetics, South Eastern Area Laboratory Services, Prince of Wales Hospital, High Street, Randwick NSW 2031, Sydney, Australia; michael.buckley{at}


Background: Recent methodological advances have improved the detection rate for dystrophin mutations, but there are no published studies that have measured the clinical utility of these protocols for carrier detection compared with conventional carrier testing protocols that use pedigree, serum creatine kinase levels and linkage analysis.

Methods and subjects: The clinical utility of a combined mutation detection protocol was measured. It involved quantitative PCR procedures followed by DNA sequence analysis for the identification of dystrophin mutation carriers in 2101 women at risk of being carriers from 348 mutation-known Duchenne or Becker muscular dystrophy pedigrees.

Results: The combined mutation detection protocol identified a mutation in 96% and 82% of index cases of Duchenne muscular dystrophy and Becker muscular dystrophy, respectively. An additional 692 (33%) potential carriers were correctly classified by the combined mutation detection protocol compared with pedigree, serum creatine kinase levels and linkage analysis. Significantly lower mutation carrier rates were identified in the mothers of isolated cases with deletion mutations than predicted from theoretical considerations, but these findings were not confirmed for duplication and DNA sequence mutations.

Conclusions: There are significant clinical benefits to be gained from a combined mutation detection protocol for carrier detection. It is recommended that mutation-specific carrier frequencies for the different classes of dystrophin mutations should be taken into account in genetic counselling practice.

  • BMD, Becker muscular dystrophy
  • CK, creatine kinase
  • D/BMD, Duchenne and Becker muscular dystrophies
  • DMD, Duchenne muscular dystrophy
  • MLPA, multiplex ligation-dependent probe amplification
  • qfPCR, quantitative fluorescent PCR technique
  • STR, short tandem repeat

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  • * These authors contributed equally.

  • Published Online First 26 January 2007

  • Funding: This study has been funded by the Muscular Dystrophy Association of New South Wales and South Eastern Area Laboratory Services.

  • Competing interests: None.