Huntington’s Disease – an inherited disorder, which will result in the lack of movement and speech, dementia and ultimately death. Earliest symptoms include lack of coordination and unsteady gait; physical abilities worse until the complete physiological breakdown of the patient’s body. Meanwhile, the mental abilities worsen as well into dementia. Overall, Huntington’s disease results in the death of brain cells.
The time span between progression and death can be between 10-25 years.
Huntington usually starts during the ages 35-45; the number of Huntington gene’s duplicates can be used to diagnose infected individuals and predict when they will develop this terrifying disease. The chances are 50-50 for an offspring to inherit the disease if a parent is affected.
Enter Nancy Wexler : a professor of Neuropsychology at Columbia University and a member of a family all inflicted with Huntington’s disease. Her grandfather died of Huntington’s, as did her mother’s three brothers. Other male members of her family were nervous of getting ill as well.
This changed when Wexler’s mother, Leonore, was diagnosed with Huntington in 1968. Walking to jury duty, a policeman once screamed at her “How can you be drunk so early in the morning? Shame on you!” But appearances were deceiving. Leonore was showing the early onset of Huntington’s disease, which led to her loosing the ability to walk, talk and feed herself until her early death on Mother’s day in 1978. Fittingly, Wexler’s PhD thesis dealt with how it feels to be at risk for the disease.
Wexler devoted the rest of her life to uncovering the causes for Huntington. However, at this time, the scientific consensus about Huntington’s disease was split, with an estimated time frame of 50-100 years for solving its causes.
Wexler felt that she need large sample sizes of affected individuals, preferably close family members as this would help to narrow down the genetic causes. Fortunately, luck struck. A Venezuelan doctor named Americo Negrette noticed the large amount of ‘drunk people’ in his town. However, a woman called him out on this assumption by pointing out that none of these drunk people smelt of alcohol.
Realizing that these people were in fact sick, Negrette began studying their cases and collecting medical information. When Wexler heard of this, she started an expedition to collect as many samples as she could from affected individuals. She was particularly interested in individuals who carried the Huntington homozygotes – children would develop Huntington early on.
Once found, all the medical information and samples were collected from these children and previous generations.
The importance of finding young children with Huntington disease and disease carriers within a family can best be summarized by quoting Wexler:
But can I tell you why? There is a part of the Huntington’s gene where the DNA is repeated over and over and over again. It spells a word called CAG, for glutamine. You need to have glutamine, but our gene just gets overly enthusiastic. It’s like an odd switch, turned [on] over and over again, so the poor gene just keeps making CAG, CAG, CAG. A normal human will have 17–24 CAGs. There was a little boy — he had nine siblings, and seven out of nine had Huntington’s — he had 120 repeats. His gene was so gigantic that you could actually identify it just by looking at its DNA sequence.
Overall, over 4000 blood samples were collected and a pedigree of over 18,000 individuals were collected. Wexler gave these blood samples to geneticists Dr. James Gusella, Dr. David Housman and Dr. Michael Conneally for further analysis, who determined in 1983 that the gene responsible for HD is located at the tip of chromosome four.
Finally, a way of diagnosing Huntington’s disease early on was found. Wexler started her reseach in 1979, and by 1983 the Huntington gene was discovered. Along the way, 14 new technologies were developed. However, until now, there is still no cure for Huntington’s disease.
Sources
http://www.laskerfoundation.org/new-noteworthy/articles/q-nancy-wexler/ (04.02.2020)
https://huntingtonstudygroup.org/events/an-interview-with-dr-nancy-wexler-discovering-the-huntington-disease-gene/ (04.02.2020)
Gusella JF, et al. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature. 1983 306:234-238.
Dean Miller, Geneticists ,Cavendish Square Publishing, LLC, 2014.
