POSSIBILITIES AND PROBLEMS IN GENOMIC DIAGNOSIS OF DUCHENNE MUSCULAR-DYSTROPHY WITH MOLECULAR PROBES

Abstract

Selected families affected with Duchenne muscular dystrophy from an extensive pedigree analysis with linked restriction fragment length polymorphisms and creatine kinase estimations are compiled to demonstrate the various counselling situations for carrier determination and prenatal diagnosis. The creatine kinase determination suffers from approximately 30% false negative values in carrier determination. The DNA analysis is limited by the uninformativity of the DNA markers and the occurrence of meiotic crossovers between the particular restriction fragment length polymorphism pattern and the Douchenne muscular dystrophy locus. The use of markers bridging the Duchenne muscular dystrophy locus, such as 754 and C7, is presently best suited for this purpose but is applicable to only a relatively small number of cases. The use of the physically closer probe, pERI 87, is much more informative although it too recombines with the Duchenne muscular dystrophys locus. DNA analysis allows prenatal diagnosis for unaffected boys from the restriction fragment length polymorphism pattern confined to the healthy grandpaternal X-chromosome in cases where the carrier status of the mother is established or in doubt. As in the case of carrier determination, crossover events and uninformativity of restriction fragment length polymorphism limit the feasibility of this approach.