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Accurate and Affordable Diagnosis of Duchenne Muscular Dystrophy


For release: Friday, April 18, 2003

Researchers have developed a simple and affordable blood test that detects the most common form of muscular dystrophy (MD) in more than 95 percent of cases.

Until now, gene mutations causing Duchenne muscular dystrophy (DMD) went undetected in roughly 35 percent of children with the disease, in spite of extensive and sometimes invasive tests that cause great discomfort and stress for patients, says study author Kevin Flanigan, M.D., of the University of Utah.

"Before, many DMD diagnoses required a muscle biopsy, which is invasive and involves some risks," Dr. Flanigan says. "Even then, some mutations were missed because of limitations with previous tests." Now, a simple blood test can detect almost all DMD cases.

The published study was funded in part by the National Institute of Neurological Disorders and Stroke and appears in the April 2003 issue of the American Journal of Human Genetics. 1

MD is a group of genetic diseases characterized by progressive weakness and degeneration of the muscles that generate movement. DMD is the most common fatal X-linked recessive disorder, which means that the disease is carried by mothers but usually appears only in boys. DMD occurs once in every 3,500 live male births. Those with the devastating disease have difficulty walking, an abnormal gait and severe limb weakness. Most are wheelchair-bound by age 7 or 8 and die by their early twenties due to respiratory or cardiac complications. To date, there is no cure.

Particular mutations in the dystrophin gene on the X chromosome cause DMD. The dystrophin gene is the largest human gene that we know of, and several different types of mutations can cause DMD.

The new test, called Single Condition Amplification/Internal Primer sequencing (SCAIP), allows clinicians and geneticists to sequence the entire dystrophin gene to find mutations that confirm DMD. "With the currently available genetic tests, we could look for only one type of mutation. Now, we can rapidly look at genetic variations in the entire gene. That's very exciting," says Dr. Flanagan.

A big hope is that the new DMD test will soon be widely available in various clinical settings. In the meantime, the SCAIP test is available to the public at the University of Utah.

The commonly used DMD test looks for missing portions of the dystrophin gene, called exons. An exon is the region within a gene that contains important parts of the genetic code. About 60 percent of DMD cases are caused by deletions in one or more exons within the dystrophin gene.

Until now, the enormous size of the dystrophin gene made it prohibitively expensive to test for mutations in the entire gene. Instead, the old test would just check "exon hotspots," catching about 98 percent of exon deletions. Other available tests detect exon duplications, which account for about 5 percent of DMD cases. But before the development of SCAIP, geneticists could not find the 35 percent of mutations that weren't exon deletions or duplications unless they obtained RNA from an invasive muscle biopsy, or used intermediate screening tests of variable sensitivity to determine specific regions of the gene to sequence from blood DNA samples.

This is a very important development, not only for diagnosing DMD, but also for finding female carriers of the disease before they pass it on to their male children. Since so many DMD mutations have been missed with previous tests, genetic counseling for the disease has been extremely difficult.

The new test will also aid researchers who are developing more effective treatments for DMD. "If we're going to treat this disease successfully, we need to be able to identify specific mutations and then tailor therapies to correct defects caused by each mutation," says Dr. Flanigan. "This test is an important first step, but there is much work that remains to be done."

Dr. Flanigan and his colleagues are coordinating with three research centers to develop an extensive patient database containing careful clinical and genetic evaluations of large groups of DMD patients. They hope that detailed genetic information about those patients will help researchers generate new hypotheses and eventually new treatments for the disease.

"As a researcher, I'm very excited about where this new method will lead us, and as a clinician, I am very happy to find a way to speed up the diagnosis of DMD and minimize the degree of uncertainty that parents face because they can't get a correct diagnosis," Dr. Flanigan says.

The NINDS is a component of the National Institutes of Health in Bethesda, Maryland, part of the U.S. Department of Health and Human Services, and is the nation's primary supporter of biomedical research on the brain and nervous system.

Reference:

1 Flanigan KM, von Niederhausern A, Dunn DM, Alder J, Mendell J, Weiss, RB. "Rapid Direct Sequence Analysis of the Dystrophin Gene." American Journal of Human Genetics, April 2003, vol. 72, no. 4, pp. 931-939.

- By Tania Zeigler



 

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Last Modified April 16, 2014