Scientists at Johns Hopkins and the University of Pennsylvania have tracked down the gene responsible for a paralyzing disease that has plagued at least eight generations of a Maryland family, the Mattinglys.
In a paper published in March's American Journal of Human Genetics, researchers report they have mapped the defective gene responsible for this illness, a form of hereditary amyotrophic lateral sclerosis (ALS), to a section of chromosome 9.
"These results bring us a major step closer to isolating the gene itself," says David Cornblath, M.D., professor of neurology. "When we do that and clone it, we can find what it does. That should help us treat not only the disease that afflicts the Mattinglys but also similar neurodegenerative disorders that affect a broader range of patients."
The Mattingly family has been afflicted for generations by a juvenile form of ALS, the paralytic condition more commonly known as Lou Gehrig's disease. These ailments kill the motor nerve cells that control muscles, leaving the muscles paralyzed and wasted.
In ALS patients, the paralysis begins to develop in mid-life or later, and typically leads to death within three to five years when respiratory muscles fail. In the Mattinglys, symptoms begin in childhood, but the paralysis, while profoundly disabling, is never fatal.
To find the gene involved, scientists used the family's extensive genealogical records, which pinpointed many of the afflicted members, and analyzed DNA in their blood samples.
Two genes already identified on chromosome 9 are potential suspects, according to Phillip Chance, M.D., formerly of Children's Hospital of Philadelphia, now professor of pediatrics at the University of Washington-Seattle. They include genes that create a calcium channel on the surface of nerve cells and are involved in a cellular suicide process.
"However, these are only two genes from a large segment of chromosome 9," says Chance, who was lead author of the study. "Geneticists haven't fully characterized this region, so there are a number other genes we will have to study."
Chance and Cornblath suspect several slightly different neurodegenerative disorders may be produced by a defect in the same gene as the Mattinglys.
"That's a problem you sometimes run into when you have to classify diseases by their symptoms, rather than their causes," Cornblath explains. "At a later date, you find out their origins are so similar they probably should be grouped together."
The study was funded by the Muscular Dystrophy Association, the March of Dimes, the National Institutes of Health, and the Myers S. Shandelman Trust. Other authors were Bruce Rabin, Barbara Crain and John Griffin of Hopkins; and Stephen Ryan, Yuan Ding and Mena Scavina of the Children's Hospital of Philadelphia and the University of Pennsylvania.
Materials provided by Johns Hopkins Medical Institutions. Note: Content may be edited for style and length.
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