3/10/03
NEW TESTS DETECT MANY
MORE DYSTROPHIN GENE FLAWS
The dystrophin gene, which carries instructions for a muscle protein
and is flawed in Duchenne and Becker muscular
dystrophies (DMD and BMD), is extremely large and complex, which
has made dystrophin genetic testing particularly challenging.
Now, MDA-supported researchers at two institutions have developed new
tests that can detect a much higher percentage of dystrophin mutations,
including some that involve very minor DNA changes that nevertheless
cause muscle disease. A third such precise dystrophin test has been
on the market since 2001.
Most commercially available tests can detect only the type of flaw
(mutation) that involves the absence of fairly large pieces of the gene
— so-called “deletion analysis” testing — which
applies to only about 60 percent of people with DMD and an uncertain
percentage of those with BMD.
It can be helpful to a family to know the precise genetic flaw to help
predict the risk of passing the disease to children, qualify for certain
research studies and, eventually, perhaps to predict the severity of
the disease or suggest specific treatments.
Baylor Test Evaluation
Carolyn Sue Richards, a molecular biologist and MDA grantee at Baylor
College of Medicine in Houston, is working on a type of dystrophin gene
analysis based on the “denaturing high performance liquid chromatography”
(DHPLC) technique.
Richards’ group wants to see how good its mutation detection
ability is by checking at least 100 boys and young men with a clinical
(symptom-based) diagnosis of DMD or BMD and a muscle biopsy result that
suggests these conditions, along with negative results on a standard
dystrophin gene deletion test.
For information on how to get into this study, which includes test
results at no cost to the family and doesn’t require travel to
Houston, contact Madhuri Hegde or Patricia Ward at the Baylor Diagnostic
Sequencing Laboratory. Phone numbers are (800) 411-GENE and (713) 798-5722,
and the e-mail address is dsl@bcm.tmc.edu.
University of Utah Test
Kevin Flanigan, an MDA research grantee at the Eccles Institute of Human
Genetics at the University of Utah in Salt Lake City, was among those
who recently developed another approach to improve dystrophin gene testing.
Flanigan says this new test is more accurate than any existing one at
detecting dystrophin flaws. MDA clinic co-director Jerry Mendell of
Ohio State University in Columbus provided patient DNA samples used
to evaluate the new procedures.
The researchers, who published an article about this new technique
in the April issue of the American Journal of Human Genetics, are using
a technique called “single condition amplification/internal primer,”
or SCAIP, sequencing.
The test is expected to become available at a cost of less than $1,000
this spring through the Human Genome Depot (www.genome.utah.edu)
at the University of Utah Health Sciences Center in Salt Lake City.
For information, call (801) 587-9540, or send e-mail to kevin.flanigan@genetics.utah.edu.
City of Hope Test
Complete dystrophin gene analysis using yet another technique, called
DOVAM, for “detection of virtually all mutations,” became
available about two years ago, with MDA support, through the City of
Hope National Medical Center in Duarte, Calif.
You can contact the Clinical Molecular Diagnostic Laboratory at www.cityofhope.org/cmdl,
or by calling (888) 826-4362. Or, you can send e-mail to cmdl@coh.org.
The cost for the specialized dystrophin testing ranges from $900 for
those who have already had a negative deletion test up to about $1,600.
