Writer Amy Harmon has a touching article in today's NY Times, profiling the yearlong adjustments faced by a 23-year-old woman who tested positive for the Huntington's gene.
In the tumultuous months that followed, Ms. Moser often found herself unable to remember what normal had once been. She forced herself to renounce the crush she had long nursed on a certain firefighter, sure that marriage was no longer an option for her. She threw herself into fund-raising in the hopes that someone would find a cure. Sometimes, she raged.
She never, she said, regretted being tested. But at night, crying herself to sleep in the dark of her lavender bedroom, she would go over and over it. She was the same, but she was also different. And there was nothing she could do.
Huntington's was one of the earliest Mendelian disorders for which scientists identified the affected gene. This has now been nearly 15 years, and identifying disease-associated genes has become a weekly occurrence. But several aspects of Huntington's facilitated finding the gene -- it is a severe disorder that strikes at midlife or earlier, but after many victims have had children, so there are many affected families with many members. This helped researchers find the gene, because there were large pedigrees for linkage analysis. Also, the disorder is caused by a repeat polymorphism -- a triplet repeat of the nucleotides CAG in the huntingtin gene. Because early genetic maps were generated by cutting the DNA and comparing the lengths of the pieces, the affected alleles were found relatively easily.
As it turns out, the severity and age at onset of the disorder is associated with the number of CAG repeats. Here's a graphic of the relationship:
The story raises an important question: DNA testing for risks and susceptibilities will increase, and how can we expect people to react to the information they receive? Huntington's is an extreme example, because it is fatal, inevitable, and uncurable. But other gene tests that are currently used clearly approach it -- the BRCA1 test for heritable breast cancer is another well-known example.
You may be unaware of just how common genetic testing has become. Currently, every child born in Wisconsin is tested for 47 heritable disorders -- many, like phenylketonuria, are disorders for which some early intervention (dietary for PKU) may ameliorate or prevent symptoms. In the near future, some genetic tests will probably become as common as blood typing. It's even conceivable that epigenetic tests will be developed, which have the potential of examining changes in methylation, expression, or other epigenetic properties over time. Those tests would be very much like cholesterol tests.
Such tests wouldn't carry the implications of a positive Huntington's test -- as certain a foreknowledge of the timing and manner of death as genetics can ever provide. A large concern that the article doesn't touch on is the high rate of suicide among those diagnosed with Huntington's. A recent study found that nearly a fourth of those approaching diagnosis or losing their independence from Huntington's have "suididal ideation", or seriously entertain thoughts of suicide (Paulsen et al. 2005). The study identifies the time immediately before diagnosis as a critical period of suicide risk. It is not obvious whether earlier genetic testing serves to reduce this risk, or whether it may displace the risk to younger and younger ages.
We're really entering an age where genetic testing will become ubiquitous, while our current reactions to such tests lie at two extremes. Some tests we don't give a second thought about, others seem like the end of the world. It is not obvious what the ideal should be for genetic testing -- how much should people attend to and care about the results of a diabetes risk assessment, or a cardiovascular risk assessment? But it seems like neither of the current extreme attitudes is really desirable for most potential diagnoses.
Maybe it would help to answer the simple question -- will genetic testing tend to make people more content, or more worried? Probably like most things, it will depend on the person. I find the linked article very affecting, because it examines one person's reaction to the test. And even after a year, with much description of her friends and family support (and lack of support), it isn't obvious whether this young woman is better off knowing or not.
Paulsen JS, Hoth KF, Nehl C, Stierman L, The Huntington Study Group. 2005. Critical periods of suicide risk in Huntington's disease. Am J. Psychiatry 162:725-731. Free online