Huntington's disease

Solo disponible en BuenasTareas
  • Páginas : 6 (1252 palabras )
  • Descarga(s) : 0
  • Publicado : 9 de junio de 2011
Leer documento completo
Vista previa del texto
Huntington’s disease (HD) is a very complex neurodegenerative disorder that affects the psychiatric health and motor skills eventually leading to death (Roze, E. Betuing, S. Deyts, C. Marcon, E. 2008). The person that takes credit for the disease is James Huntington whose paper about the disease was published in 1872 (Bates, G., Harper, P.S., & Jones, L.2002). The roots of HD can be traced backto East Anglin Europe. Ironically however, the area which lead to the discovery of the gene that causes HD was a small village on Lake Maracaibo in Venezuela. In this village there was a large concentration of people living with Huntington’s disease. After doing extensive studies here there was a pedigree drawn that included over 10,000 people with HD, over 100 of those living with HD. This studyshowed that those that were homozygous for HD were no more affected than those that were heterozygous. Further proving what was already speculated, that HD is autosomal dominant. These studies also lead to the discovery of the gene that causes HD.
In 1993 the cause of HD was found to be a mutation in a CAG repeat expansion in exon one of the Huntington’s disease gene (Runne, H, Kuhn, A, & Wild,E.J. 2007). CAG codes for a relatively large 350 kDa protein, called Huntington (Bates, G. et al. 2002). Since this discovery there has been a nonstop effort to discover the mechanisms through which the protein product creates such a devastating disease. Even thought the cause of HD is now clear at a genetic level the processes that determine the symptoms and eventually lead to death are far frombeing understood. Along with neuronal loss, a sustained activation of inflammatory processes, which manifest as an increase in the number of astrocytes and in a buildup of microglia. This occurs in the neostriatum, cortex, globus pallidus, and the adjoining white matter of HD brains. A common feature of many neurodegenerative disorders is microinflammation (Runne, H. et al 2007).
The discovery ofthe gene that causes HD started with genetic linking which was depended upon for gene-mapping projects. Genetic linkage is the co-inheritance of two genes because of their close proximity on a chromosome. It was soon found that HD could be linked with G8. The ability to do this enabled doctors to do presymptomatic testing for people who were at risk of having HD and for prenatal diagnoses forunborn children at risk of having HD. This linkage using the marker G8 also directed scientists to the short arm on chromosome four. Once this was discovered it enabled genes in the critical region to be cloned, sequenced, and tested for mutations. After ten years of cloning by six different groups the gene causing HD was finally discovered (Bates, G. et al 2002).
Soon after the discovery of the CAGrepeat studies were released that all patients with HD had a CAG repeat that was definitely larger than that of the normal population. Perhaps one of the most significant findings was that exactly 3’ to the CAG repeat there was another CCG repeat. In most people with HD there is an enlargement 3’ from the CAG codon where the polymorphism of CCG takes place, but this is not always the case. Whenthis polymorphism does not occur the primers that overlap with this end of the repeat will fail to amplify. When this occurs it can lead to a misdiagnoses of HD (Bates, G. et al 2002).
The earliest signs of HD manifest as psychiatric disorders. Some of these include depression, anxiety, irritability, and sleep disorders along with frontal and subcortical cognitive disorders. These symptoms arelater followed with choreic movements, dystonia, and rigidity. Peripherally weight loss is also common in HD (Roze, E. et al 2008).
Genotpically and phenotypically speaking if a person has HD and they conceive with another person that does not carry the gene for HD, there is a fifty percent chance that their offspring will inherit the disease. Many studies have been done to investigate the...
tracking img