Huntington's test tale proves our unpredictability

Within a year of the identification in 1993 of the huntingtin gene, which in mutant form causes the fatal brain disorder Huntington's disease, geneticists devised a test to detect the mutation, and offered it to families with a history of the disease.

The development of a test to predict family members' individual risk, and to diagnose the disease, was just the beginning of a surprising tale of human unpredictability, according to Canadian geneticist Dr Michael Hayden, of the University of British Columbia, in Vancouver.

Huntington's is an autosomal dominant disorder, one of an unusual class of inherited diseases in which a repeated DNA motif in the gene's promoter spontaneously expands between generations. The severity, and age of onset of the disorder, varies with the number of repeats.

Because symptoms typically appear after 40, before 1994, there was no way a parent could know whether they had passed a mutant variant of the gene to his or her own children -- or if they would develop the disease themselves. It was widely expected that young adults in affected families would seek to have the test before deciding to have families of their own.

But Hayden says that's not the case. In the nine years since the test was developed, the main users have been around the age of 40 -- the typical age of onset of first symptoms.

It's rarely used in a family-planning context. Between 10 and 15 per cent of individuals in their 60s have volunteered to be tested, and several people in their 90s have been tested.

These individuals were completely asymptomatic, even though several were over the 35-repeat threshold that would normally predict they wold develop the disease, indicating that genetic or environmental factors other than the huntingtin gene influence individual risk.

Hayden says most people are taking the test in mid-life to help them make career, financial and retirement decisions: "They want to know whether to hire a motor home or a nurse."

Another surprise, he says, is that 25 per cent of individuals tested, who are displaying early symptoms of Huntington's, have no family history of the disorder. The high rate of de novo mutation has surprised geneticists.

Overall, only 18 per cent of at-risk individuals in families with a history of Huntington's have chosen to take the predictive test. Hayden says this is surprising, given that under Canada's health system does not discriminate against at-risk individuals if screening confirms they are likely to develop the disease.

Another surprise is that the majority of individuals being tested are female: "Men and women differ in their response to information about genetic risks to health."