Sunday, 20 May 2012

Huntington Disease

Huntington Disease 
           Yap Wei Chien 42722937

Huntington disease (HD) is an inherited neurodegenerative genetic disorder of the central nervous system that causes wastage of brain cell that lead to emotional problem, muscle coordination, cognitive declination and psychiatric problems. This disorder usually occur in people that were born with a defective gene, however the onset of Huntington disease usually occurs in middle age. The early symptoms of HD are depression, poor muscle coordination, loss of memory and decline in mental capacity. The abnormal involuntary movement cause by HD is known as chorea or Huntington’s chorea which develop involuntary jerking and twitching movement on the individual. As severity of HD prolong as time, individual would lost ability to walk and speak. It could lead to personality changes and decline in reasoning and thinking abilities of the individual.

Huntington’s disease is an incurable disease that has affected over 100,000 people worldwide, on top of that the likely to affect 300,000 individual to develop symptoms in their lifetime. HD is inherited as an autosomal dominant condition. Individuals with adult-onset of Huntington disease usually have a life span about 20years after it struck. There’s no way to slow down or inhibit the severity of the disease however medication could help to reduce the effect of certain symptoms.

            Huntington disease occur due to the mutation of HTT gene which provides instructions for making a protein known as huntingtin, however the function of the protein is yet to be known but it play a crucial role in nerve cell (neurons) in brain. The gene that responsible for Huntington disease lies on the fourth chromosome whereby the alteration of DNA sequences of CAG (cytosine-adenine-guanine) that self-duplicating in individual. This process known as trinucleotide repeat disorders which cause by the length of repeated section of a gene exceeding a normal range, therefore in HD’s individuals there are 40-100 repeated CAG segment in their DNA.  CAG is the genetic code for amino acid glutamine that resulting in production of polyglutamin tract (polyQ tract) and repeated part of the gene (polyQ region). The increase of CAG segments lead to production of elongated huntingtin protein. The altered form (mHtt) increase the decay rate of certain types of neurons. The defect protein is cut into fragments which bind in neurons which lead to dysfunction and death of neurons in certain areas of the brain where sign and symptoms of HD occurs.

Classification of the trinucleotide repeat, and resulting disease status, depends on the number of CAG repeats
Repeat count
Disease status
Reduced Penetrance
+/- Affected
Full Penetrance

In recent scientific discovery, an enzymes known as histone deacetylase complexes (HDACs) could be activated as a positive agent for HD’s disease mutation which its exacerbate the disease-causing mutation in cells. It found that blocking these HDACs with experimental drugs greatly reduced the risk of mutation and it slows down the mutation process therefore likelihood to reduce the progression of HD. According to Professor Robert Lahue of National University of Ireland Galway’s Centre for Chromosome Biology said that “ongoing mutation in the brain of HD patients are thought to drive progression of the disease” and he emphasized that HDAC inhibitors are still in experimental and their development to potential drugs is still some way off. If succeeded, the implication would not only applicable to Huntington disease whereas other neurological disorders cause by similar mutation could be overcome.

1.      Debra Collin, M.S, CGC (1999), “Genetics of Huntington diseases’, viewed on 13th March 2012 []

2., “Huntington’s Disease’, viewed on 13th March 2012 []

3.      Walker FO (2007). "Huntington's disease". Lancet 369 (9557): 218–28

4.       Katsuno M, Banno H, Suzuki K et al (2008). "Molecular genetics and biomarkers of polyglutamine diseases".Curr. Mol. Med. 8 (3): 221–34.

5.      Nance MA, Myers RH (2001). "Juvenile onset Huntington's disease—clinical and research perspectives". Ment Retard Dev Disabil Res Rev 7 (3): 153–7

6.      Public Library of Science. Medical News Today (2012, February 22). "New Discovery In Fight Against Huntington's Disease." Viewed on 13th March 2012 []

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