Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-5cf477f64f-tgq86 Total loading time: 0 Render date: 2025-04-06T06:25:46.460Z Has data issue: false hasContentIssue false

57 - Huntington's disease

from Part X - Other neurodegenerative diseases

Published online by Cambridge University Press:  04 August 2010

M. Flint Beal ,
Anthony E. Lang  and
Albert C. Ludolph
By
Christoph M. Kosinski  and
Bernhard Landwehrmeyer
M. Flint Beal
Affiliation:
Cornell University, New York
Anthony E. Lang
Affiliation:
University of Toronto
Albert C. Ludolph
Affiliation:
Universität Ulm, Germany
Christoph M. Kosinski
Affiliation:
Department of Neurology, University Hospital Aachen, Germany
Bernhard Landwehrmeyer
Affiliation:
Department of Neurology, University of Ulm, Germany
Get access

Summary

Introduction

The description by George Huntington in 1872 of the disease that has subsequently borne his name is remarkable for its clarity and comprehensiveness (Huntington, 1872). It was not the first description of the disorder (see, for instance, Charles Oscar Waters, 1842, and Johan Christian Lund, 1860) (Waters, 1842; Lund, 1860), but it stands out as the first full delineation of the condition as a specific disease entity, quite separate from other forms of chorea. Huntington's paper was given at Middleport, Ohio, and published later in the Philadelphia journal, The Medical and Surgical Reporter. One can do no better than quote it here:

The hereditary chorea, as I shall call it, is confined to certain and fortunately a few families, and has been transmitted to them, an heirloom from generations away back in the dim past. It is spoken of by those in whose veins the seeds of the disease are known to exist, with a kind of horror, and not at all alluded to except through dire necessity, when it is mentioned as ‘that disorder’. It is attended generally by all the symptoms of common chorea, only in an aggravated degree hardly ever manifesting itself until adult or middle life, and then coming on gradually but surely, increasing by degrees, and often occupying years in its development, until the hapless sufferer is but a quivering wreck of his former self. (…) There are three marked peculiarities in this disease: 1. Its hereditary nature. 2. A tendency to insanity and suicide.[…]

Type
Chapter
Information
Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
 , pp. 847 - 860
Publisher: Cambridge University Press
Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Albin, R. L., Young, A. B. & Penney, J. B. (1989). The functional anatomy of basal ganglia disorders. Trends Neurosci., 12, 366–75CrossRefGoogle ScholarPubMed
Andrew, S. E., Goldberg, Y. P., Kremer, B.et al. (1993). The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nat. Genet., 4, 398–403CrossRefGoogle ScholarPubMed
Andrew, S. E., Goldberg, Y. P., Kremer, B.et al. (1994a). Huntington disease without CAG expansion: phenocopies or errors in assignment?Am. J. Hum. Genet., 54, 852–63Google Scholar
Andrew, S. E., Goldberg, Y. P., Theilmann, J., Zeisler, J. & Hayden, M. R. (1994b). A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: implications for diagnostic accuracy and predictive testing. Hum. Mol. Genet., 3, 65–7CrossRefGoogle Scholar
Ashizawa, T., Wong, L. J., Richards, C. S., Caskey, C. T. & Jankovic, J. (1994). CAG repeat size and clinical presentation in Huntington's disease. Neurology, 44, 1137–43CrossRefGoogle ScholarPubMed
Bamford, K. A., Caine, E. D., Kido, D. K., Cox, C. & Shoulson, I. (1995). A prospective evaluation of cognitive decline in early Huntington's disease: functional and radiographic correlates. Neurology, 45, 1867–73CrossRefGoogle ScholarPubMed
Barron, L. H., Rae, A., Holloway, S., Brock, D. J. & Warner, J. P. (1994). A single allele from the polymorphic CCG rich sequence immediately 3′ to the unstable CAG trinucleotide in the IT15 cDNA shows almost complete disequilibrium with Huntington's disease chromosomes in the Scottish population. Hum. Mol. Genet., 3, 173–5CrossRefGoogle ScholarPubMed
Bauer, P., Laccone, F., Rolfs, A.et al.(2004). Trinucleotide repeat expansion in SCA17/TBP in white patients with Huntington's disease-like phenotype. J. Med. Genet., 41, 230–2CrossRefGoogle ScholarPubMed
Beal, M. F. (1995). Aging, energy, and oxidative stress in neurodegenerative diseases. Ann. Neurol., 38, 357–66CrossRefGoogle ScholarPubMed
Beenen, N., Buttner, U. & Lange, H. W. (1986). The diagnostic value of eye movement recordings in patients with Huntington's disease and their offspring. Electroencephalogr. Clin. Neurophysiol., 63, 119–27CrossRefGoogle ScholarPubMed
Behrens, P. F., Franz, P., Woodman, B., Lindenberg, K. S. & Landwehrmeyer, G. B. (2002). Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation. Brain, 125, 1908–22CrossRefGoogle ScholarPubMed
Bots, G. T. & Bruyn, G. W. (1981). Neuropathological changes of the nucleus accumbens in Huntington's chorea. Acta Neuropathol. (Berl.), 55, 21–2CrossRefGoogle ScholarPubMed
Boutell, J. M., Thomas, P., Neal, J. W.et al. (2004). Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin. Hum. Mol. Genet., 1999, 1647Google Scholar
Brandt, J., Strauss, M. E., Larus, J., Jensen, B., Folstein, S. E. & Folstein, M. F. (1984). Clinical correlates of dementia and disability in Huntington's disease. J. Clin. Neuropsychol., 6, 401–12CrossRefGoogle Scholar
Brandt, J., Bylsma, F., Gross, R., Stine, O., Ranen, N. & Ross, C. (1996). Trinucleotide repeat length and clinical progression in Huntington's disease. Neurology, 46, 531–5CrossRefGoogle ScholarPubMed
Brinkman, R. R., Mezei, M. M., Theilmann, J., Almqvist, E. & Hayden, M. R. (1997). The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size. Am. J. Hum. Genet., 60, 1202–10Google ScholarPubMed
Browne, S. E., Ferrante, R. J. & Beal, M. F. (1999). Oxidative stress in Huntington's disease. Brain Pathol., 9, 147–63CrossRefGoogle ScholarPubMed
Bruyn, G. W. (1979). [Huntington's chorea]. Tijdschr. Ziekenverpl., 32, 101–5Google Scholar
Butters, N., Wolfe, J., Granholm, E. & Martone, M. (1986). An assessment of verbal recall, recognition and fluency abilities in patients with Huntington's disease. Cortex, 22, 11–32CrossRefGoogle ScholarPubMed
Bylsma, F. W., Rebok, G. W. & Brandt, J. (1991). Long-term retention of implicit learning in Huntington's disease. Neuropsychologia, 29, 1213–21CrossRefGoogle ScholarPubMed
Cepeda, C., Ariano, M. A., Calvert, C. R.et al. (2001). NMDA receptor function in mouse models of Huntington disease. J. Neurosci. Res., 66, 525–39CrossRefGoogle ScholarPubMed
Cha, J. H.. (2000). Transcriptional dysregulation in Huntington's disease. Trends Neurosci., 23, 387–92CrossRefGoogle ScholarPubMed
Cha, J. H., Kosinski, C. M., Kerner, J. A.et al. (1998). Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc. Natl Acad. Sci. USA, 95(11), 6480–5CrossRefGoogle ScholarPubMed
Cha, J. H., Frey, A. S., Alsdorf, S. A.et al. (1999). Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease. Phil. Trans. R. Soc. Lond. B Biol. Sci., 354, 981–9CrossRefGoogle ScholarPubMed
Chen, M., Ona, V. O., Li, M.et al. (2000). Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of huntington disease. Nat. Med., 6, 797–801Google Scholar
Chen, S., Ferrone, F. A. & Wetzel, R. (2002). Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation. Proc. Natl Acad. Sci., USA, 99, 11884–9CrossRefGoogle ScholarPubMed
Chong, S. S., Almqvist, E., Telenius, H.et al. (1997). Contribution of DNA sequence and CAG size to mutation frequencies of intermediate alleles for Huntington disease: evidence from single sperm analyses. Hum. Mol. Genet., 6, 301–9CrossRefGoogle ScholarPubMed
Claes, S., Zand, K., Legius, E.et al. (1995). Correlations between triplet repeat expansion and clinical features in Huntington's disease. Arch. Neurol., 52, 749–53CrossRefGoogle ScholarPubMed
Critchley, E. M., Clark, D. B. & Wikler, A. (1967). An adult form of acanthocytosis. Trans. Am. Neurol. Assoc., 92, 132–7Google ScholarPubMed
Crossman, A. R.. (1987). Primate models of dyskinesia: the experimental approach to the study of basal ganglia-related involuntary movement disorders. Neuroscience, 21, 1–40CrossRefGoogle Scholar
Cummings, C. J. & Zoghbi, H. Y. (2000). Trinucleotide repeats: mechanisms and pathophysiology. Annu. Rev. Genom. Hum. Genet., 1, 281–328CrossRefGoogle ScholarPubMed
Curra, A., Agostino, R., Galizia, P., Fittipaldi, F., Manfredi, M. & Berardelli, A. (2000). Sub-movement cueing and motor sequence execution in patients with Huntington's disease. Clin. Neurophysiol., 111, 1184–90CrossRefGoogle ScholarPubMed
Curtis, A. R., Fey, C., Morris, C. M.et al. (2001). Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat. Genet., 28, 350–4CrossRefGoogle ScholarPubMed
Danek, A., Tison, F., Rubio, J., Oechsner, M., Kalckreuth, W. & Monaco, A. P. (2001). The chorea of McLeod syndrome. Mov. Disord., 16, 882–9CrossRefGoogle ScholarPubMed
Davies, S., Turmaine, M., Cozens, B.et al. (1997). Formation of neuronal intranuclear inclusions (NII) underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90, 537–48CrossRefGoogle Scholar
Davis, M. B., Bateman, D., Quinn, N. P., Marsden, C. D. & Harding, A. E. (1994). Mutation analysis in patients with possible but apparently sporadic Huntington's disease. Lancet, 344, 714–17CrossRefGoogle ScholarPubMed
Boo, G., Tibben, A., Hermans, J., Maat, A. & Roos, R. A. (1998). Subtle involuntary movements are not reliable indicators of incipient Huntington's disease. Mov. Disord., 13, 96–9CrossRefGoogle Scholar
Dedeoglu, A., Kubilus, J. K., Yang, L.et al. (2003). Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J. Neurochem., 85, 1359–67CrossRefGoogle ScholarPubMed
DiFiglia, M., Sapp, E., Chase, K.et al. (1997). Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science, 277, 1990–3CrossRefGoogle ScholarPubMed
Dunah, A. W., Jeong, H., Griffin, A.et al. (2002). Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science, 296, 2238–43CrossRefGoogle ScholarPubMed
Duyao, M., Ambrose, C. & Myers, R. (1993). Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat. Genet., 4, 387–92CrossRefGoogle ScholarPubMed
Farrer, L. A. (1985). Diabetes mellitus in Huntington disease. Clin. Genet., 27(1), 62–7CrossRefGoogle ScholarPubMed
Feigin, A., Kieburtz, K., Bordwell, K.et al. (1995). Functional decline in Huntington's disease. Mov. Disord., 10, 211–14CrossRefGoogle ScholarPubMed
Ferrante, R. J., Andreassen, O. A., Jenkins, B. G.et al. (2000). Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J. Neurosci., 20, 4389–97CrossRefGoogle Scholar
Ferrante, R. J., Kubilus, J. K., Lee, J.et al. (2004). Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice. J. Neurosci., 23, 9418–27CrossRefGoogle Scholar
Folstein, S. E., Jensen, B., Leigh, R. J. & Folstein, M. F. (1983). The measurement of abnormal movement: methods developed for Huntington's disease. Neurobehav. Toxicol. Teratol., 5, 605–9Google ScholarPubMed
Forno, L. S. & Norville, R. L. (1979). Ultrastructure of the neostriatum in Huntington's and Parkinson's disease. Adv. Neurol., 23, 123–39Google Scholar
Friedlander, R. M. (2003). Apoptosis and caspases in neurodegenerative diseases. N. Engl. J. Med., 348, 1365–75CrossRefGoogle ScholarPubMed
Garcia Ruiz, P. J., Gomez-Tortosa, E., del Barrio, A.et al. (1997). Senile chorea: a multicenter prospective study. Acta Neurol. Scand., 95, 180–3CrossRefGoogle ScholarPubMed
Gellera, C., Meoni, C., Castellotti, B.et al. (1996). Errors in Huntington disease diagnostic test caused by trinucleotide deletion in the IT15 gene. Am. J. Hum. Genet., 59, 475–7Google ScholarPubMed
Georgiou, N., Phillips, J. G., Bradshaw, J. L., Cunnington, R. & Chiu, E. (1997). Impairments of movement kinematics in patients with Huntington's disease: a comparison with and without a concurrent task. Mov. Disord., 12, 386–96CrossRefGoogle ScholarPubMed
Goldberg, Y. P., Andrew, S. E., Theilmann, J.et al. (1993). Familial predisposition to recurrent mutations causing Huntington's disease: genetic risk to sibs of sporadic cases. J. Med. Genet., 30, 987–90CrossRefGoogle ScholarPubMed
Gusella, J. F., Wexler, N. S., Conneally, P. M.et al. (1983). A polymorphic DNA marker genetically linked to Huntington's disease. Nature, 306, 234–8CrossRefGoogle ScholarPubMed
Gusella, J. F., Tanzi, R. E., Bader, P. I.et al. (1985). Deletion of Huntington's disease-linked G8 (D4S10) locus in Wolf–Hirschhorn syndrome. Nature, 318, 75–8CrossRefGoogle ScholarPubMed
Haines, J. L. & Conneally, P. M. (1986). Causes of death in Huntington disease as reported on death certificates. Genet. Epidemiol., 3, 417–23CrossRefGoogle ScholarPubMed
Hardie, R. J., Pullon, H. W., Harding, A. E.et al. (1991). Neuroacanthocytosis. A clinical, haematological and pathological study of 19 cases. Brain, 114(Pt 1A), 13–49Google ScholarPubMed
Hefter, H., Homberg, V., Lange, H. W. & Freund, H. J. (1987). Impairment of rapid movement in Huntington's disease. Brain, 110(3), 585–612CrossRefGoogle ScholarPubMed
Heinsen, H., Strik, M., Bauer, M.et al. (1994). Cortical and striatal neurone number in Huntington's disease. Acta Neuropathol., 88, 320–33CrossRefGoogle ScholarPubMed
Hickey, M. A. & Chesselet, M.-F. (2003). Apoptosis in Huntington's disease. Prog. Neuropsychopharmacol. Biol. Psychiatr., 27, 255–65CrossRefGoogle ScholarPubMed
Higgins, J. J., Patterson, M. C., Papadopoulos, N. M., Brady, R. O., Pentchev, P. G. & Barton, N. W. (1992). Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome). Neurology, 42, 194–8CrossRefGoogle Scholar
Hockly, E., Richon, V. M., Woodman, B., et al. (2003). Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Proc. Natl Acad. Sci., USA, 100, 2041–6CrossRefGoogle Scholar
Hoffmann, J. (1888). Über Chorea chronica progressiva (Huntingtonsche Chorea, Chorea hereditaria). Virchow's Archiv für Pathol. Anat., 111, 513–48CrossRefGoogle Scholar
Holbert, S., Denghien, I., Kiechle, T.et al. (2001). The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis. Proc. Natl Acad. Sci., USA, 98, 1811–16CrossRefGoogle ScholarPubMed
Huntington, G. (1872). On chorea. Med. Surg. Rep., 26, 317–21Google Scholar
Huntington Study Group (1996). Unified Huntington's Disease Rating Scale: reliability and consistency. Mov. Disord., 11, 136–42CrossRef
Huntington's Disease Collaborative Research Group (1993). A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell, 72, 971–83CrossRef
Jelgersma, G. (1908). Die anatomischen Veränderungen bei Paralysis agitans und chronischer Chorea. Verh. Ges. Dtsch. Naturforsch. Ärzt., 2, 383–8Google Scholar
Kambouris, M., Bohlega, S., Al Tahan, A. & Meyer, B. F. (2000). Localization of the gene for a novel autosomal recessive neurodegenerative Huntington-like disorder to 4p15.3. Am. J. Hum. Genet., 66, 445–52CrossRefGoogle ScholarPubMed
Kehoe, P., Krawczak, M., Harper, P. S., Owen, M. J. & Jones, A. L. (1999). Age of onset in Huntington disease: sex specific influence of apolipoprotein E genotype and normal CAG repeat length. J. Med. Genet., 36, 108–11Google ScholarPubMed
Kieburtz, K., MacDonald, M., Shih, C.et al. (1994). Trinucleotide repeat length and progression of illness in Huntington's disease. J. Med. Genet., 31, 872–4CrossRefGoogle ScholarPubMed
Kirkwood, S. C., Siemers, E., Hodes, M. E., Conneally, P. M., Christian, J. C. & Foroud, T. (2000). Subtle changes among presymptomatic carriers of the Huntington's disease gene. J. Neurol. Neurosurg. Psychiatr., 69, 773–9CrossRefGoogle ScholarPubMed
Koller, W. C. & Trimble, J. (1985). The gait abnormality of Huntington's disease. Neurology, 35, 1450–4CrossRefGoogle ScholarPubMed
Koroshetz, W. J., Jenkins, B. G., Rosen, B. R. & Beal, M. F. (1997). Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann. Neurol., 41, 160–5CrossRefGoogle ScholarPubMed
Kovtun, I. V. & McMurray, C. T. (2001). Trinucleotide expansion in haploid germ cells by gap repair. Nat. Genet., 27, 407–11CrossRefGoogle ScholarPubMed
Kremer, B., Almqvist, E., Theilmann, J.et al. (1995). Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes. Am. J. Hum. Genet., 57, 343–50Google ScholarPubMed
Kremer, B., Clark, C. M., Almqvist, E. W.et al. (1999). Influence of lamotrigine on progression of early Huntington disease: a randomized clinical trial. Neurology, 53, 1000–11CrossRefGoogle ScholarPubMed
Kremer, H. P. & Roos, R. A. (1992). Weight loss in Huntington's disease. Arch. Neurol., 49, 349CrossRefGoogle ScholarPubMed
Landwehrmeyer, G. B., McNeil, S. M., Dure, L. S.et al. (1995). Huntington's Disease Gene: regional and cellular expression in brain of normal and affected individuals. Ann. Neurol., 37, 218–30CrossRefGoogle ScholarPubMed
Lanska, D. J., Lanska, M. J., Lavine, L. & Schoenberg, B. S. (1988). Conditions associated with Huntington's disease at death. A case-control study. Arch. Neurol., 45, 878–80CrossRefGoogle ScholarPubMed
Lasker, A. G. & Zee, D. S. (1997). Ocular motor abnormalities in Huntington's disease. Vision Res., 37, 3639–45CrossRefGoogle ScholarPubMed
Lasker, A. G., Zee, D. S., Hain, T. C., Folstein, S. E. & Singer, H. S. (1998). Saccades in Huntington's disease: slowing and dysmetria. Neurology, 38, 427–31CrossRefGoogle Scholar
Leeflang, E. P., Zhang, L., Tavare, S.et al. (1995). Single sperm analysis of the trinucleotide repeats in the Huntington's disease gene: quantification of the mutation frequency spectrum. Hum. Molec. Genet., 4, 1519–26CrossRefGoogle ScholarPubMed
Li, J. L., Hayden, M. R., Almqvist, E. W.et al. (2003). A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS study. Am. J. Hum. Genet., 73, 682–7CrossRefGoogle Scholar
Li, S. H., Schilling, G., Young, W.3et al. (1993). Huntington's disease gene (IT15) is widely expressed in human and rat tissues. Neuron, 11, 985–93CrossRefGoogle ScholarPubMed
Li, S. H., Cheng, A. L., Zhou, H.et al. (2002). Interaction of Huntington disease protein with transcriptional activator Sp1. Mol. Cell. Biol., 22, 1277–87CrossRefGoogle ScholarPubMed
Losekoot, M., Bakker, B., Laccone, F., Stenhouse, S. & Elles, R. (1999). A European pilot quality assessment scheme for molecular diagnosis of Huntington's disease. Eur. J. Hum. Genet., 7, 217–22CrossRefGoogle ScholarPubMed
Louis, E. D., Marder, K., Moskowitz, C. & Greene, P. (1999). Arm elevation in Huntington's disease: dystonia or levitation?Mov. Disord., 14, 1035–83.0.CO;2-D>CrossRefGoogle ScholarPubMed
Louis, E. D., Anderson, K. E., Moskowitz, C., Thorne, D. Z. & Marder, K. (2000). Dystonia-predominant adult-onset Huntington disease: association between motor phenotype and age of onset in adults. Arch. Neurol., 57, 1326–30CrossRefGoogle ScholarPubMed
Lund, J. C. (1860). Chorea St Vitus Dance in Saetersdalen. In Quoted by Orbeck 1, ed. p. 137
MacMillan, J. C., Snell, R. G., Tyler, A.et al. (1993). Molecular analysis and clinical correlations of the Huntington's disease mutation. Lancet, 342, 954–958CrossRefGoogle ScholarPubMed
Mahadevan, M., Tsilfidis, C., Sabourin, L.et al. (1992). Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science, 255, 1253–5CrossRefGoogle ScholarPubMed
Mandich, P.,Di Maria, E., Bellone, E., Ajmar, F. & Abbruzzese, G. (1996). Molecular analysis of the IT15 gene in patients with apparently ‘sporadic’ Huntington's disease. Eur. Neurol., 36, 348–52CrossRefGoogle ScholarPubMed
Mangiarini, L., Sathasivam, K., Seller, M.et al. (1996). Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell, 87, 493–506CrossRefGoogle Scholar
Marder, K., Zhao, H., Myers, R. H.et al. (2000). Rate of functional decline in Huntington's disease. Huntington Study Group. Neurology, 54, 452–58CrossRefGoogle ScholarPubMed
Margolis, R. L., O'Hearn, E., Rosenblatt, A.et al. (2001). A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion. Ann. Neurol., 50, 373–80CrossRefGoogle ScholarPubMed
Mars, H., Lewis, L. A., Robertson, A. L. Jr., Butkus, A. & Williams, G. H. Jr. (1969). Familial hypo-beta-lipoproteinemia: a genetic disorder of lipid metabolism with nervous system involvement. Am. J. Med., 46, 886–900CrossRefGoogle ScholarPubMed
McComas, A. J., Sica, R. E. & Toyonaga, K. (1978). Incidence, severity, and time-course of motoneurone dysfunction in myotonic dystrophy: their significance for an understanding of anticipation. J. Neurol. Neurosurg. Psychiatr., 41, 882–93CrossRefGoogle ScholarPubMed
Moore, R. C., Xiang, F., Monaghan, J.et al. (2001). Huntington disease phenocopy is a familial prion disease. Am. J. Hum. Genet., 69, 1385–8CrossRefGoogle ScholarPubMed
Morales, L. M., Estevez, J., Suarez, H., Villalobos, R., Chacin, D. B. & Bonilla, E. (1989). Nutritional evaluation of Huntington disease patients. Am. J. Clin. Nutr., 50, 145–50CrossRefGoogle ScholarPubMed
Myers, R. H., Vonsattel, J. P., Stevens, T. J.et al. (1988). Clinical and neuropathologic assessment of severity in Huntington's disease. Neurology, 38, 341–7CrossRefGoogle ScholarPubMed
Myers, R. H., Sax, D. S., Koroshetz, W. J.et al. (1991). Factors associated with slow progression in Huntington's disease. Arch. Neurol., 48, 800–4CrossRefGoogle ScholarPubMed
Myers, R. H., MacDonald, M. E., Koroshetz, W. J.et al. (1993). De novo expansion of a (CAG)n repeat in sporadic Huntington's disease. Nat. Genet., 5, 168–73CrossRefGoogle ScholarPubMed
Nance, M. A. (1998). Huntington disease: clinical, genetic, and social aspects. J. Geriatr. Psychiatry Neurol., 11, 61–70CrossRefGoogle ScholarPubMed
Nucifora, F. C.., Sasaki, M., Peters, M. F.et al. (2001). Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science, 291, 2423–8CrossRefGoogle ScholarPubMed
Oepen, G., Clarenbach, P. & Thoden, U. (1981). Disturbance of eye movements in Huntington's chorea. Arch. Psychiatr. Nervenkr., 229, 205–13Google ScholarPubMed
Panas, M., Avramopoulos, D., Karadima, G., Petersen, M. B. & Vassilopoulos, D. (1999). Apolipoprotein E and presenilin-1 genotypes in Huntington's disease. J. Neurol., 246, 574–7CrossRefGoogle ScholarPubMed
Panov, A. V., Gutekunst, C.-A., Leavitt, B.et al. (2002). Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat. Neurosci., 5, 731–6CrossRefGoogle ScholarPubMed
Penney, J. B. Jr., Young, A. B., Shoulson, I.et al. (1990). Huntington's disease in Venezuela: 7 years of follow-up on symptomatic and asymptomatic individuals. Mov. Disord., 5, 93–9CrossRefGoogle ScholarPubMed
Penney, J. B.., Vonsattel, J. P., MacDonald, M. E., Gusella, J. F. & Myers, R. H. (1997). CAG repeat number governs the development rate of pathology in Huntington's disease. Ann. Neurol., 41, 689–92CrossRefGoogle ScholarPubMed
Perutz, M. (1996). Glutamine repeats and inherited neurodegenerative diseases: molecular aspects. Curr. Opin. Struct. Biol., 6, 848–58CrossRefGoogle ScholarPubMed
Phillips, J. G., Bradshaw, J. L., Chiu, E., Teasdale, N., Iansek, R. & Bradshaw, J. A. (1996). Bradykinesia and movement precision in Huntington's disease. Neuropsychologia, 34, 1241–45CrossRefGoogle ScholarPubMed
Pickering, D. S., Thomsen, C., Suzdak, P. D.et al. (1993). A comparison of two alternatively spliced forms of a metabotropic glutamate receptor coupled to phosphoinositide turnover. J. Neurochem., 61, 85–92CrossRefGoogle ScholarPubMed
Pratley, R. E., Salbe, A. D., Ravussin, E. & Caviness, J. N. (2000). Higher sedentary energy expenditure in patients with Huntington's disease. Ann. Neurol., 47, 64–703.0.CO;2-S>CrossRefGoogle ScholarPubMed
Quinn, N. & Schrag, A. (1998). Huntington's disease and other choreas. J. Neurol., 245, 709–16CrossRefGoogle ScholarPubMed
Ranen, N., Stine, O., Abbot, M.et al. (1995). Anticipation and instability of IT-15 (CAG)n repeats in parent-offspring pairs with Huntington disease. Am. J. Hum. Genet., 57, 593–602Google ScholarPubMed
Reiner, A., Albin, R. L., Anderson, K. D., D'Amato, C. J., Penney, J. B. & Young, A. B. (1988). Differential loss of striatal projection neurons in Huntington disease. Proc. Natl Acad. Sci., USA, 85, 5733–7CrossRefGoogle ScholarPubMed
Roizin, L., Stellar, S., & Liu, J. (1979). Neuronal nuclear-cytoplasmic changes in Huntingtons chorea: electron microscope investigations. In Advance in Neurology, Huntington's Disease, ed. N. Wexler & A. Barbeau, New York: Raven Press. pp. 195–22
Roos, R. A., Pruyt, J. F., Vries, J. & Bots, G. T. (1985). Neuronal distribution in the putamen in Huntington's disease. J. Neurol. Neurosurg. Psychiatr., 48, 422–5CrossRefGoogle ScholarPubMed
Rosenblatt, A., Brinkman, R. R., Liang, K. Y. (2001). Familial influence on age of onset among siblings with Huntington disease. Am. J. Med. Genet., 105, 399–403CrossRefGoogle ScholarPubMed
Ross, C. A. (2002). Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disorders. Neuron, 35, 819–22CrossRefGoogle ScholarPubMed
Rubinsztein, D. C., Leggo, J., Barton, D. E. & Ferguson-Smith, M. A. (1993). Site of (CCG) polymorphism in the HD gene. Nat. Genet., 5, 214–15CrossRefGoogle ScholarPubMed
Rubinsztein, D. C., Leggo, J., Coles, R.et al. (1996). Phenotypic characterization of individuals with 30–40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36–39 repeats. Am. J. Hum. Genet., 59, 16–22Google ScholarPubMed
Rubinsztein, D. C., Leggo, J., Chiano, M.et al. (1997). Genotypes at the GluR6 kainate receptor locus are associated with variation in the age of onset of Huntington disease. Proc. Natl Acad. Sci., USA, 94, 3872–6CrossRefGoogle ScholarPubMed
Sanberg, P. R., Fibiger, H. C. & Mark, R. F. (1981). Body weight and dietary factors in Huntington's disease patients compared with matched controls. Med. J. Aust. 1, 407–9Google ScholarPubMed
Saudou, F., Finkbeiner, S., Devys, D. & Greenberg, M. (1998). Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell, 95, 55–66CrossRefGoogle Scholar
Schapira, A. H. (1999). Mitochondrial involvement in Parkinson's, Huntington's disease, hereditary spastic paraplegia and Friedreich's ataxia. Biochem. Biophys. Act., 1410, 99–102Google ScholarPubMed
Scherzinger, E., Lurz, R., Turmaine, M.et al. (1997). Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell, 90, 549–58CrossRefGoogle ScholarPubMed
Schilling, G., Sharp, A. H., Loev, S. J.et al. (1995). Expression of the Huntington's disease (IT15) protein product in HD patients. Hum. Mol. Genet., 4, 1365–71CrossRefGoogle ScholarPubMed
Schubotz, R., Hausmann, L., Kaffarnik, H., Zehner, J. & Oepen, H. (1976). Fatty acid patterns and glucose tolerance in Huntington's chorea. Res. Exp. Med. (Berl.), 167(3), 203–15CrossRefGoogle ScholarPubMed
Schwarz, M., Fellows, S. J., Schaffrath, C. & Noth, J. (2001). Deficits in sensorimotor control during precise hand movements in Huntington's disease. Clin. Neurophysiol., 112, 95–106CrossRefGoogle ScholarPubMed
Sharp, A. H., Loev, S. J., Schilling, G.et al. (1995). Widespread expression of Huntington's disease gene (IT15) protein product. Neuron, 14, 1065–74CrossRefGoogle ScholarPubMed
Shinotoh, H., Calne, D. B., Snow, B.et al. (1994). Normal CAG repeat length in the Huntington's disease gene in senile chorea. Neurology, 44, 2183–4CrossRefGoogle ScholarPubMed
Shoulson, I. (1981). Huntington disease: functional capacities in patients treated with neuroleptic and antidepressant drugs. Neurology, 31, 1333–5CrossRefGoogle ScholarPubMed
Shoulson, I. & Fahn, S. (1979). Huntington disease: clinical care and evaluation. Neurology, 29, 1–3CrossRefGoogle ScholarPubMed
Shoulson, I., Odoroff, C., Oakes, D.et al. (1989). A controlled clinical trial of baclofen as protective therapy in early Huntington's disease. Ann. Neurol., 25, 252–9CrossRefGoogle ScholarPubMed
Snell, R. G., MacMillan, J. C., Cheadle, J. P.et al. (1993). Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nat. Genet., 4, 393–7CrossRefGoogle ScholarPubMed
Snowden, J., Craufurd, D., Griffiths, H., Thompson, J. & Neary, D. (2001). Longitudinal evaluation of cognitive disorder in Huntington's disease. J. Int. Neuropsychol. Soc., 7, 33–44CrossRefGoogle ScholarPubMed
Steffan, J. S., Kazantsev, A., Spasic-Boskovic, O.et al. (2000). The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl Acad. Sci., USA, 97, 6763–8CrossRefGoogle ScholarPubMed
Steffan, J. S., Bodai, L., Pallos, J.et al. (2001). Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature, 413, 739–43CrossRefGoogle ScholarPubMed
Tanaka, M., Machida, Y., Niu, S.et al. (2004). Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat. Med., 10, 148–54CrossRefGoogle Scholar
Thompson, P. D., Berardelli, A., Rothwell, J. C.et al. (1988). The coexistence of bradykinesia and chorea in Huntington's disease and its implications for theories of basal ganglia control of movement. Brain, 111(2), 223–44CrossRefGoogle ScholarPubMed
Tian, J. R., Zee, D. S., Lasker, A. G. & Folstein, S. E. (1991). Saccades in Huntington's disease: predictive tracking and interaction between release of fixation and initiation of saccades. Neurology, 41, 875–81CrossRefGoogle ScholarPubMed
Trottier, Y., Biancalana, V. & Mandel, J. L. (1994). Instability of CAG repeats in Huntington's disease: relation to parental transmission and age of onset. J. Med. Genet., 31, 377–82CrossRefGoogle ScholarPubMed
Vugt, J. P., Hilten, B. J. & Roos, R. A. (1996). Hypokinesia in Huntington's disease. Mov. Disord., 11, 384–88CrossRefGoogle ScholarPubMed
Vonsattel, J. P., Myers, R. H., Stevens, T. J., Ferrante, R. J., Bird, E. D. & Richardson, E. Jr. (1985). Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol., 44, 559–77CrossRefGoogle ScholarPubMed
Vuillaume, I., Meynieu, P., Schraen-Maschke, S., Destee, A. & Sablonniere, B. (2000). Absence of unidentified CAG repeat expansion in patients with Huntington's disease-like phenotype. J. Neurol. Neurosurg. Psychiatr., 68, 672–5CrossRefGoogle ScholarPubMed
Waters, C. O. (1842). In Practice in Medicine, ed. R. Dunglison. Philadelphia: Lee and Blanchard. p. 312
Wellington, C. L., Brinkman, R. R., Kusky, J. & Hayden, M. R. (1997). Toward understanding the molecular pathology of Huntington's disease. Brain Pathol., 7, 979–1002CrossRefGoogle ScholarPubMed
Westphal, C. (1883). Über eine dem Bilde der cerebrospinalen grauen Degeneration ähnlichen Erkrankung des centralen Nervensystems ohne anatomischen Befund, nebst einigen Bemerkungen über paradoxe Contractionen. Arch. Psychiatr. Nervenkr., 14, 187–94CrossRefGoogle Scholar
Yang, W., Dunlap, J. R., Andrews, R. B. & Wetzel, R. (2002). Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells. Hum. Mol. Genet., 11, 2905–17CrossRefGoogle ScholarPubMed
Young, A. B., Shoulson, I., Penney, J. B.et al. (1986). Huntington's disease in Venezuela: neurologic features and functional decline. Neurology, 36, 244–9CrossRefGoogle ScholarPubMed
Zeron, M. M., Hansson, O., Chen, N.et al. (2002). Increased sensitivity to N-methyl-D-asparta te receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron, 33, 849–60CrossRefGoogle Scholar
Zuhlke, C., Riess, O., Schroder, K.et al. (1993). Expansion of the (CAG)n repeat causing Huntington's disease in 352 patients of German origin. Hum. Mol. Gene., 2, 1467–9Google ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×