Gene defect for muscle disorder identified.
Since 1982, a small cadre of scientists has gathered family histories of people with early-onset torsion dystonia torsion dystonia Neurology An AD, possibly also AR condition most common in Jews, onset age 5 to 16 Clinical Gait defects, involuntary contractions and distortion of spine, hands, feet, hips, and eventually neck; lesions typically start in one body region, usually , a crippling disorder that causes the muscles to contract, twist, or sometimes jerk involuntarily. The researchers also took blood samples from the families and painstakingly probed their DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. for genetic clues that might reveal dystonia's origin.
There were few other options. Unlike neuromuscular diseases such as Parkinson's or Huntington's, dystonia dystonia /dys·to·nia/ (-to´ne-ah) dyskinetic movements due to disordered tonicity of muscle.dyston´ic
dystonia musculo´rum defor´mans is difficult to track in the body. "There is no part of the brain that degenerates [in dystonia], so there is no easy way to see what's going on What's Going On is a record by American soul singer Marvin Gaye. Released on May 21, 1971 (see 1971 in music), What's Going On reflected the beginning of a new trend in soul music. ," says Laurie J. Ozelius, a geneticist ge·net·i·cist
A specialist in genetics.
a specialist in genetics.
geneticist at Harvard University Medical School in Boston.
Their efforts have now paid off. Ozelius and her colleagues report in the September Nature Genetics the discovery of a mutation that underlies the disease. It's in a gene named DYT DYT Dayton (Ohio)
DYT Don't You Think?
DYT Dublin Youth Theatre
DYT Dynamo Youth Theatre (UK) 1.
The researchers examined blood samples from 267 unrelated people with no history of severe dystonia and from members of 68 families with clear symptoms of the disorder. The mutation appears in none of the control group and in all of the dystonia patients' families.
Ozelius and her collaborators also identified a mysterious protein, torsinA, which the DYT1 gene encodes. A defective version of torsinA predisposes a person to dystonia.
If one parent has the disease, which is genetically dominant, each child should have a 50-50 chance of inheriting it. Yet researchers were puzzled for years because fewer than half of the children showed symptoms of dystonia. Indeed, recent work reveals that only 30 to 40 percent of people with a mutated DYT1 ever show its effects.
This oddity led researchers to suspect that environmental factors combine with the mutation to trigger the disease. The answer may lie in the role of torsinA. While the protein's function is unclear, scientists see links between it and known actors in the cell. For example, torsinA resembles compounds called heat-shock proteins, which are expressed when a cell faces fever or injury.
Researchers now plan to reexamine re·ex·am·ine also re-ex·am·ine
tr.v. re·ex·am·ined, re·ex·am·in·ing, re·ex·am·ines
1. To examine again or anew; review.
2. Law To question (a witness) again after cross-examination. family data from carriers of the mutated gene. Many such families report incidents of trauma or high fever in a youngster who later developed severe dystonia, says study coauthor Susan B. Bressman, a neurologist at Columbia University. However, since virtually all young children encounter such stresses, the researchers don't know Don't know (DK, DKed)
"Don't know the trade." A Street expression used whenever one party lacks knowledge of a trade or receives conflicting instructions from the other party. whether a connection will emerge.
An age-related decline in the risk of symptoms also poses a puzzle. "Once you reach the age of 22, you're generally home free," Bressman says.
The fact that dystonia doesn't strike in later adulthood raises biological questions, she says. Does the body do something to block the mutation in later years, or does the mutation have a time-dependent shutoff shut·off
1. A device that shuts something off.
2. A stoppage; a cessation. switch?
"It's a fascinating discovery. It will whet the appetite of neuroscientists," says Giovanna Spinella of the National Institute of Neurological Disorders and Stroke The National Institute of Neurological Disorders and Stroke is a part of the U.S. National Institutes of Health.
The NINDS conducts and supports research on brain and nervous system disorders. Created by the U.S. in Bethesda, Md.
The DYT1 mutation is rare, occurring in no more than I in 5,000 people in the United States. Among Jews of European descent, it occurs in as many as 1 in 1,000 people, Bressman says.
The discovery of the mutation opens the way for a simple test to distinguish a child with severe dystonia from one with cerebral palsy or one of several milder types of dystonia. Severe dystonia is seldom fatal, but it can render an individual wheelchair-bound.
Future research will involve rodents with and without mutated DYT1, Ozelius says. Researchers in the laboratory will also be able to expose tissue cultures with and without the mutated gene to hot temperatures and stress to determine whether torsinA behaves like a heat-shock protein.