Mutant gene is not always a killer.

The gene behind the neurological disorder Huntington's disease continues to surprise investigators. After finding the gene in 1993, researchers discovered that the deadly disease results only when the gene contains an abnormally large number of occurrences of a small sequence of DNA. If a person has too many of these so-called CAG repeats, Huntington's usually strikes. The more repeats the person's gene has, the earlier the disease tends to start. While Huntington's usually strikes adults, the disease has shown up in teenagers.

Recently, investigators have tried to pin down exactly how many CAG repeats it takes to turn the Huntington gene into a killer. Though most patients have 40 to 90 repeats, physicians have identified Huntington's patients with as few as 36.

Yet a set of 36 repeats, even 37, 38, or 39, in the Huntington gene is not always a death sentence. Among 178 people with 30 to 40 CAG repeats in the gene, 10 individuals having 36 to 39 repeats had no signs of the disease, even though they were all more than 67 years old, report David C. Rubinsztein of the East Anglian Medical Genetics Service in Cambridge, England, and his coworkers in the July American Journal of Human Genetics.

One man with 39 CAG repeats lived until the age of 95. Two physical exams during his latter years revealed no symptoms of Huntington's, and an autopsy did not find the brain cell loss typical of the disease. Such cases suggest that factors besides the number of CAG repeats can, in rare instances, determine whether a person will suffer from Huntington's, says Christopher A.

Ross of Johns Hopkins University in Baltimore, a survey coauthor. Unearthing those cofactors, suggests Ross, may help explain how CAG repeats produce disease and point the way to treatments for Huntington's.