An inherited brain disorder (Huntington's disease): the rare case where a gene almost decides
Bates et al., Nature Reviews Disease Primers, 2015
- How it was tested
- A review of everything known about the disease: genetics, mechanism, diagnosis, treatment.
- What came out
- The disease is caused by an expanded repeat of three DNA “letters” (CAG) in the HTT gene. Inheritance is dominant: one changed copy from one parent is enough. So each child of a carrier has a 50% chance of inheriting the changed gene, and the chance is separate for every child, like a coin toss. The disease usually begins in the prime of adult life, progresses gradually and affects movement, thinking and behaviour. At the time of the review there were no drugs that changed its course.
- What it means
- Diseases like this created the idea of a “genetic sentence”. But they are rare, and their logic can't be carried over to heart attacks or diabetes. A limit: even here there is variation, because the length of the repeat affects when and how the disease appears.
What Huntington's disease does to the brain
- 1
The striatum, highlighted in purple. A deep region that controls movement. The first changes appear here: already at the earliest stage visible under a microscope, about half of the nerve cells in the caudate nucleus are lost, and up to 95% at the late stage. Hence the involuntary jerking movements and clumsiness.
- 2
The cortex, the folded outer layer of the brain. It thins too, and early, most of all in the strip that controls movement and sensation. Which parts of the cortex are affected differs from person to person, and this explains why symptoms vary so much: in some people movement problems dominate, in others problems with thinking or mood.
