REVISION NEEDED: Huntington`s Disease

HUNTINGTON 'S DISEASE

HUNTINGTON 'S DISEASE

Author 's Name

University HUNTINGTON 'S DISEASE

Huntington 's disease is a degenerative brain disease that is transmitted by autosomal dominant inheritance . It was first described by George Huntington a resident of Ohio who had made the observation in a group of people living in Long Island . It has a prevalence of 5 in 100 000 individuals5 . It is found equally in both sexes and has no geographical boundaries . The average age of presentation is between thirty and forty years of age and the

lifespan can range from 15-25 years1 . Signs and symptoms are those of a movement dis with psychiatric manifestations eventually leading to dementia . Hence this disease is also called Huntington 's chorea because of the jerky , purposeless movements traveling from one part of the body to the other associated with this disease5 . Distonia , rigidity and seizures may also be present and the signs and symptoms vary from individual to individual

The pathophysiology of the disease is complex but has been discovered to be a mutation in HD gene present on the short arm of chromosome four that is 4p 16 .39 (MacDonald et al . 1992 . This mutation results in expansion of the CAG sequence of DNA that leads to a synthesis of a polyglutamine (polyQ ) that causes degeneration of nerve cells . It was found out that the CAG sequence in normal genes repeats itself about 10-35 times whereas in mutant DNA the CAG sequence multiplies to 36-120 times . Also CAG extensions occurred more in males where as females had an ability to suppress them maybe through their sex chromosomes (Kovtun et al 2000 . The HD gene codes a protein huntingtin that is located in various nerve cells both in the nucleus and cytoplasm and is thought to control the transcription of brain derived neurotrophic factor (BDNF which is a protein located in the striatal areas of the brain . This protein is associated with normal functioning of the brain and mutations of huntingtin result in deficient production of BDNF (Zuccato et al 2001 )7 . The mutated huntingtin causes an increase in apopain and caspace activity that eventually leads to cell death . Cell death mainly was due to impairment of the cytoskeleton anchoring mechanism and also due to faulty transport of the mitochondria (Gutekunst et al 1995 . According to a study by Ambrose et al (1994 ) revealed that HD locus has 67 exons and their size is averagely 138 bp (ranging between 48bp - 341 bp . The locus spans to 180 kb . In patients it is present in two forms , the normal one and a mutant form (protein size is approximated to 350 kD in human cells (Trottier et al , 1995 . Studies by Trottier et al (1995 showed that HD protein is present in preikarya and nerve endings of certain neuropils , neurons and varicosities . Polyadenylated forms were observed in different tissues suggesting their important role in cell loss

It has been shown that not only the striatum but also other areas of the brain...