Huntington's disease (HD) is a familial and rare inherited neurological disorder with a prevalence of 5-8 cases per 100,000 worldwide. This makes HD the most common inherited neurodegenerative disorder (Fahn, 2005). HD is passed from parent to child in autosomal dominant fashion. Each child of an HD parent has a 50% chance of inheriting HD. Both sexes are affected equally. It is amongst the first inherited genetic disorders where an accurate test is now available. The disease complex is ascribed to George Huntington who in 1872 described the clinical and neurological manifestations. The neuronal degeneration causes uncontrolled and abnormal body movements called chorea, mental dysfunction, personality changes, and emotional disturbances. Neuropathologically, HD is associated with the death of GABAergic medium sized spiny projection neurons in the caudate nucleus and to neurons in other brain regions. The HD gene, huntingtin (htt), is located on the short arm of chromosome 4, contains N-terminal 18 amino acid-encoding open reading frame, followed by expanded CAG trinucleotide repeat which encodes variable length of poly glutamine tract, and large C-terminal region (>3,100 amino acids). The length of the HD CAG repeats is the primary determinant of the age at which clinical symptoms will appear (Persichetti et al., 1994). Although it is commonly known that the HD polyglutamate tract leads to formation of intracellular inclusions in cytoplasm and/or nucleus in a number of tested species, the correlation of the inclusion with neurotoxicity has been extremely variable. However, the increased number of glutamine is accompanied by the propensity of full-length htt protein to misfold and aggregate; therefore HD belongs to the class of protein misfolding/aggregation disorders. Early HD symptoms are seen in a person's forties, but can occur at any age. Symptoms include mood swings, depression, irritability, difficulties in learning and remembering, and in decision making. As the disease progresses, concentration becomes difficult and daily tasks of maintaining one's self are all but gone; also individuals have difficulty feeding and swallowing. Death in HD typically occurs around 15 years after motor onset due to complications of the disorder, such as aspiration pneumonia. Presymptomic testing is available for individuals who are at risk for carrying the HD gene. There is no known treatment that alters the course of the disease, but symptoms can be managed.
- CAG repeats
- Huntingtin (htt)
- Medium spiny neurons (MSNs)
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)