Gene Discovery Linked to SIDS : Research: UCI team, in identifying the cause of ‘startle disease,’ also may have led the way to a better understanding of the more common syndrome blamed for infant deaths.
Raising hope of better understanding sudden infant death syndrome, researchers at the UC Irvine have discovered a mutated gene that causes a rare inherited disease.
The UCI study, published today in Nature Genetics, identifies the flawed gene that causes hyperekplexia, also known as “startle disease” or “stiff baby syndrome,” in which victims respond to loud noises or sudden touches with muscle spasms and rigidity, sometimes causing infants to stop breathing.
While hyperekplexia is not often fatal and can be controlled with medication, scientists say information learned about the disruption of chemical pathways could lead to a better understanding of SIDS, a far more common killer of infants that also halts their breathing.
“They found a mutation in the gene that affects communication from one nerve cell to the other. It is possibly the same thing that is going on in SIDS,” said Nancy Wexler, president of the Hereditary Disease Foundation, a nonprofit organization based in Santa Monica.
“Many times, nature teaches us about the more common disorders like SIDS from understanding the very rare ones, like stiff baby syndrome,” she said.
The study was funded with grants from the Hereditary Disease Foundation and the National Center for Human Genome Research in Bethesda, Md.
Wexler said that the “very imaginative” shortcut method that the UCI researchers employed in finding the hyperekplexia-linked gene could be used as a laboratory model for other gene searches.
John Wasmuth, UCI professor of biological chemistry and principal investigator in the gene study, acknowledged there is little demand for research to cure hyperekplexia. He said it occurs in about one in 40,000 individuals, infants and adults alike, and can be effectively treated with the drug clonazepam.
But he said the disease can be fatal in infants, and muscle rigidity accompanying the disease can cause older people to fall and injure themselves.
Most intriguing, Wasmuth said, is the possibility that the same kind of genetic defect that causes breathing cessation in hyperekplexia victims may cause SIDS.
Wasmuth said that SIDS, unlike hyperekplexia, usually is not an inherited disease. But he said a genetic mutation could occur in SIDS infants after conception.
He said UCI researchers next will seek to compare the faulty gene in hyperekplexia victims with the same gene in babies who die from SIDS to see if there are similar mutations.
The mutant gene in people suffering from hyperekplexia, he said, impairs codes for a receptor molecule in the brain that cause errors in the transmission of chemical signals that control reflexes such as breathing.
Wasmuth said in the last decade only 14 or 15 genes have been discovered worldwide that are responsible for inherited diseases.
His laboratory participated in multi-center studies that in 1991 discovered the gene that causes familial colon cancer and last March found the gene that causes Huntington’s disease.
Wasmuth said the discovery of the hyperekplexia-linked gene is the first for which UCI can take total credit for the laboratory side of the genetic research.
Researchers at the University of Texas Health Science Center in San Antonio and the University of Western Ontario in London, Canada, participated in the study, Wasmuth said, by identifying adults with family histories of the disease and providing samples of their white blood cells to UCI’s genetic researchers.
The mutated gene that causes hyperekplexia was discovered about two months ago by postdoctoral researcher Rita Shiang after an 18-month search by a team of four UCI scientists, he said.
She found the “one-in-three-billion” possible genetic mutations in the human body that triggered the disease, he said. Her field of investigation was restricted to Chromosome 5, which has been the primary focus of UCI’s genetic research. Each human cell contains 23 pairs of chromosomes.
Ultimately, Wasmuth said, Shiang found that one of the 1,500 smallest components of a particular gene was out of the normal DNA sequence in everyone who suffered from hyperekplexia. “It is very exciting,” Wasmuth said of the finding. He observed that Nature Genetics, a British scientific journal, is widely read by genetic scientists and “takes only very hot stuff.”
