Duchenne’s muscular dystrophy
Background: One form of inherited muscular dystrophy, Duchenne’s, is X-linked and therefore affects primarily males. The symptoms of Duchenne’s muscular dystrophy (DMD) include progressive and severe skeletal muscle weakness. A common mutation associated with DMD is a deletion of one or more exons in the dystrophin gene. These deletions can be detected by restriction enzyme digestion and Southern blotting using a combination of probes that will bind to multiple dystrophin exons.
Case A: Jean and Bill have three sons, ages 12, 8, and 7, and a daughter, age 6. The oldest son and daughter are healthy, but the two younger sons are exhibiting symptoms of muscle weakness consistent with early muscular dystrophy. Jean knows that she has a family history of muscular dystrophy, but she does not know whether she is a carrier of the disease gene. She seeks DNA testing to determine whether her younger sons may have inherited the form of the dystrophin gene associated with Duchenne’s muscular dystrophy (DMD).
To carry out a Southern blot, each DNA sample is digested with Hind III, run on an agarose gel, and then blotted with the dystrophin gene probe (DMD probe).
DNA samples:
Jean (mother)
Oldest son (unaffected)
Daughter
8-year old son (possibly affected)
7-year old son (possibly affected)
Questions:
- Based on the number and sizes of the fragments bound by the probe, determine the status of each of the individuals tested.
- What conclusions can you draw from these results?
- What is the molecular basis of this disease, and why does this result in the observed gel patterns?
- What issues are raised by this type of testing?