Sponsored by the U.S. Department of Energy Human Genome Program
Human Genome News Archive Edition
Human Genome News, January 1994; 5(5)
International teams reported in the December 1 issue of Nature Genetics the discovery of the defective gene and exact mutations responsible for the dominant neurologic disorder hyperekplexia. The teams were led by John Wasmuth (University of California, Irvine); Stephen Ryan and Peter O'Connell (University of Texas Health Science Center, San Antonio); and Angelica Hahn (University of Western Ontario).
The defective gene, located on chromosome 5, encodes one subunit of the inhibitory glycine receptor. Individuals with this condition, also called "stiff baby syndrome" or "startle disease," respond to loud noises or unexpected touching with sometimes life-threatening spasms and muscle rigidity. The research on hyperekplexia was supported by grants from the National Center for Human Genome Research (NCHGR), the Hereditary Disease Foundation, the Morrison Trust, and the National Institute for Neurologic Disease and Stroke.
Hyperekplexia affects about 1 in 40,000 people. Although the condition is not life threatening in adults, the spasms and muscle ridigity can cause serious injuries from falls. Infants with the condition often die from apnea (cessation of breathing), also believed to cause death in many cases of Sudden Infant Death Syndrome.
Because hyperekplexia can be treated effectively with the benzodiazepine drug clorazepam, the gene's discovery is more important to the basic understanding of neurological disorders than for any immediate clinical benefit. "Understanding how and why the mutations we've identified in this gene result in a neurologic disorder will help scientists better understand the normal role of this important neurotransmitter pathway," Wasmuth said.
Hyperekplexia is the first inherited neurologic disorder found to be caused by a mutation directly affecting a neurotransmitter receptor in the central nervous system. "It really is the ultimate of finding a needle in a haystack one base pair change in three billion," Wasmuth said. He attributed the success to several factors, including outstanding cooperation and open exchange of information and resources among the collaborating groups; the work of Rita Shiang, the postdoctoral investigator in his laboratory who actually discovered the mutation; and accurate, pre-existing maps of chromosome 5.
Discovery of the hyperekplexia gene marks the third time in 2 years that Wasmuth's laboratory has played a role in identifying the gene responsible for a genetic disorder. His laboratory, part of the collaborative research group that discovered the Huntington's Disease gene, also cooperated with Ray White's laboratory at the University of Utah in isolating the familial polyposis gene, which causes a predisposition for developing colon cancer.
Wasmuth's laboratory was designated by NCHGR as the 16th National Center for Human Genome Science and Technology and given the specific mission of making a detailed physical map of chromosome 5. The center will also work toward identifying other chromosome 5 disease genes, including those that cause Treacher Collins syndrome (a common developmental disorder) and two types of muscular dystrophy.
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Human Genome Program, U.S. Department of Energy, Human Genome News (v5n5).
The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.
Published from 1989 until 2002, this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research.