Direct method for prenatal diagnosis and carrier detection in Duchenne/Becker muscular dystrophy using the entire dystrophin cDNA.
DNA sequence polymorphisms (RFLPs) have been widely used as genetic markers for identification of the X chromosome that carries the mutation for Duchenne muscular dystrophy (DMD) in affected families, but serious limitations and pitfalls are associated with this approach [Darras et al., 1987]. The complementary DNA (cDNA) of the DMD gene has recently been isolated and shown to detect partial gene deletions in a large proportion of patients [Koenig et al., 1987]. Two prenatal studies are presented to illustrate how the unambiguous identification of deletion mutations by cDNA probes permits direct DNA-based diagnoses with high accuracy and in otherwise uninformative families. In a single proband family, DNA marker analysis had determined that the Xp21 chromosomal region present in the affected male was also carried by a male fetus in a subsequent pregnancy. Analysis of this family's DNA with probes covering the entire 14 kb cDNA revealed a small deletion in the affected male that was not present in the fetus nor in the mother. In the second family the fetus was a female deletion carrier identified by comparing intensities of restriction fragments. Since 1/3 of all DMD patients are thought to result from new mutations and most families have only single affected males, the cloned cDNA probes now available are likely to revolutionize DNA-based diagnostic studies in this disorder. More reliable, more rapid and less expensive than linkage studies with DNA polymorphisms, this method will be informative in the more than 50% of DMD/BMD cases that have deletion mutations.
D002872:Chromosome Deletion; D004247:DNA / Q000235:genetics*; D016189:Dystrophin; D005260:Female; D005796:Genes; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014960:X Chromosome
D016189:Dystrophin; D009124:Muscle Proteins; D004247:DNA