Disease Genes

The Gene for Huntington Disease

IMAGE CREDIT: Kevin Roth and Robert Schmidt, Washington University, St. Louis, MO, USA

Brain section from a patient with Huntington's disease showing dilatation of ventricles and atrophy of caudate nucleus

Introduction

Huntington Disease (HD) is degenerative brain disorder that is, essentially, a terminal illness. Although it is a genetic disorder, the onset of the disease occurs in mid-life, typically between the ages of 30 and 35. Once the onset occurs, those with HD may undergo "depression, mood swings, forgetfulness, clumsiness, involuntary twitching and lack of coördination." (www.hdsa.org) The disease was first described as a hereditory disease in 1872 by Dr. George Huntington and is usually mentioned as a "classic hereditory disease." Debilating and devastating as this disease is, much promise was held for a cure for the disease when, in 1993, the gene for the disease was mapped. However, in 2003, the disease is still uncurable.

Popular Press and Huntington Disease

Newspaper articles and commentaties about Huntington Disease are failry common due to the crippling nature of the disease. HD has come into the news recently, in June of 2002, when a mother took two of her sons' lives after they had started showing symptoms of the disease. She and her children had watched her husband's painful death just years before, and the two boys decided they didn't want to die that way. "It was terrible," James Scott, a sibling of the two boys, said. "How he kept living like that, I don't know. It was agonizing." (Atlanta Journal-Constitution, 6/10/2002). Obviously, this disease raises question of assisted suicide, as well as genetic screening for those that might have the disease.

News of the discovery of the disease came on March 31, 1993, when researchers at MIT found the gene that is the cause of HD. Since then, there has been much optimism for a cure, a point which has been grasped by many in the media. As expected, the media's portrayal of science's progress with this disease hasn't been too outlandish due to the sensitive nature of HD. It would be safe to say that media-types would be much more likely to sensationalize a "fat gene" or a "smart gene" than a gene that produces such devastating results. However, by no means does this imply that the media has been perfectly accurate in all circumstances. The contradictions between the media and the scientific community are discussed in the next section.

A Scientific Look

Huntington Disease was diagnosed as a hereditary disease as early as 1872, but only recent developments in the fields of genetics and genomics have provided hope of a cure. Specifically, HD is "associated with increases in the length of a CAG triplet repeat present in a gene called 'huntingtin' located on chromosome 4p16.3" (OMIM website). Because of the early categorization of the disease, clinical studies of the disease date back to 1959 and range to the present day. The clinical trials show the first major controversy between media and science. Giordani et al. (1995) found that, within families that had the dominant gene for Huntington disease, there were no early neuropsychologic indications between genotype positive and genotype negative individuals. Much has been alluded to in the press about these early signs as such indicators.

Biochemically, Schwarcz et al. (1988) found that the HD brain has the capacity to produce endogenous quinolic acid at an abnormally high rate. Quinolic acid is often referred to as an "excitotoxin" due to its ability to excite neurons in a manner similar to that of neurotransmitters, while providing eventual toxic affects.

More science to come!!!!

OMIM's database on Huntington Disease (HD)