Measurement of the clinical utility of a combined mutation detection protocol in carriers of Duchenne and Becker muscular dystrophy.
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
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.
Taylor
Peter J
PJ
Molecular and Cytogenetics Unit, Department of Haematology and Genetics, South Eastern Area Laboratory Services, Prince of Wales Hospital, Randwick, Sydney, Australia.
Maroulis
Sarah
S
Mullan
Glenda L
GL
Pedersen
Robyn L
RL
Baumli
Aurora
A
Elakis
George
G
Piras
Sara
S
Walsh
Corrina
C
Prósper-Gutiérrez
Benito
B
De La Puente-Alonso
Fernando
F
Bell
Christopher G
CG
Mowat
David R
DR
Johnston
Heather M
HM
Buckley
Michael F
MF
D005260:Female; D006580:Genetic Carrier Screening; D006579:Heterozygote; D006801:Humans; D008297:Male; D009035:Mothers; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*