UCI Study Ties Infant-Killing Disease to Gene : Medicine: Researchers hope the results will help improve diagnoses and lead to treatments for spinal muscular atrophy.
UC Irvine researchers report that they have identified a genetic abnormality they believe causes spinal muscular atrophy, the most common genetic cause of death in infants.
“This is a long-anticipated finding that should quickly improve accuracy in diagnosis of the forms of SMA,” said Donald S. Wood, director of science technology for the Muscular Dystrophy Assn. “Most important, it will accelerate our continuing search for a form of treatment for SMA.”
No treatment now exists.
The disorder, which in its most severe form is uniformly fatal before the age of 2, affects about 20,000 Americans, including between 200 and 300 currently in Orange County, making it the second most common lethal genetic disorder after cystic fibrosis. It affects one in 10,000 births, but about one in 40 adults carries the defective gene.
The identification of the gene is reported by a team led by UC Irvine molecular biologist John J. Wasmuth in the January issue of the journal Nature Genetics, released today.
Wasmuth said Thursday that discovery will allow couples with a family history of the disease to determine if their offspring would have a likelihood of being stricken.
“Couples can now have a prenatal test that can determine fairly accurately whether another child will have the disease,” said Wasmuth, 48, a Mission Viejo resident whose team has been working on this project for about three years. He estimated the accuracy of the testing at about 60%.
The next step will be to develop a test that identifies carriers of the gene, Wasmuth said. Unfortunately, “most people don’t know they are a carrier until they have a child who dies from the disease,” Wasmuth said.
Although Wasmuth called the finding a “very, very big step,” he said discovering a cure for SMA is still a long way off.
“It is only a first step. It really says nothing about a cure,” Wasmuth said. “When we completely understand what goes wrong in the disease, we might be able to do something to correct the abnormality.”
His team believes that the disorder is caused by the loss of segments of a gene called XS2G3 on chromosome 5, one of the 23 pairs of chromosomes that make up the human genetic blueprint.
They studied DNA from 29 patients with the most severe form of the disease, called Type I SMA, and compared it to DNA from 235 healthy people. They found that 17 of the 29 patients were missing fragments of XS2G3 in both copies of the gene (one from each parent). In contrast, only two of the 235 healthy people--both of them known carriers of the disorder--were missing fragments of the gene, and only in one copy.
The Muscular Dystrophy Assn.’s Wood speculated that fragments are missing in all 29 patients but that researchers were unable to detect them in 12 cases because of the extreme complexity of that area of chromosome 5.
He added that several other teams are expected to report soon on research that may verify the UC Irvine team’s findings.
There are four distinct forms of SMA, varying in severity. Each are degenerative in nature, affecting the nerve cells of the spinal cord and preventing them from working properly, Wasmuth said.
As the disease progresses, all muscle function eventually is lost, including the diaphragm, and children typically die from suffocation, Wasmuth said.
“The signals are not sent to the muscle cells properly, and the cells then begin to waste and degenerate,” Wasmuth said.
Type I, known as Werdnig-Hoffman disease, is characterized by generalized muscle weakness, trouble swallowing and sucking, breathing distress and paralysis of legs and arms within three months after birth. It is usually fatal by age 2.
It made headlines in the sports world last spring when the 9-month-old son of California Angels pitcher Mark Leiter died on the opening day of the season of the Type I version, considered the most severe.
Type II strikes in the first 6 months to 3 years and is usually fatal during childhood. Types III and IV strike later in life. Although they are crippling, they do not affect life span. The researchers speculate that the severity of the disease is controlled by the amount of material missing from the gene.
Other members of the team included molecular biologists Arthur H. M. Burghes of Ohio State University and Louise R. Simard of the Hopital Sainte-Justine in Montreal.
Times staff writer Len Hall contributed to this story.
