Spinocerebellar ataxias

Duyckaerts C, Durr A, Cancel G, Brice A. Nuclear inclusions in spinocerebellar ataxia type 1. Acta Neuropathol Berl 1999 97 201-207. 

Holmberg M, Duyckaerts C, Durr A, Cancel G, Gourfinkel An I, Damier P, Faucheux B, Trottier Y, Hirsch EC, Agid Y, Brice A. Spinocerebellar ataxia type 7 (SCA7) a neurodegenerative disorder with neuronal intranuclear inclusions. Hum Mol Genet 1998 7 913-918. 

Spinocerebellar ataxia type 1 [8] SCA1 6p23 paternal 6-39... 

Durr, A., Stevanin, G., Cancel, G. et al Spinocerebellar ataxia 3 and Machado-Joseph disease clinical, molecular and neuropathological features. Ann. Neurol. 39 490-499, 1996. 

Ikeuchi, T., Takano, H., Koide, R. et al Spinocerebellar ataxia type 6 CAG repeat expansion in alA voltage-dependent calcium channel gene and clinical variations in Japanese population. Ann. Neurol 42 879-884,1997. 

Huntington disease (HD) is the prototypic disease caused by expansion of unstable GAG repeat. It primarily affects striatal neurons. It is a mid-life onset disorder characterized by unvoluntary movements (chorea), personality changes and dementia that progress to death within 10-20 years of onset. There are currently no treatment to delay or prevent appearance of the symptoms in the patients. Other diseases in this class include spinocerebellar ataxias (SCA) 1, 2, 3 (also known as Machado-Joseph disease, MJD), 6, and 7, DRPLA, and spinobulbar muscular atrophy (SMA, also known as Kennedy s disease) (Zoghbi and Orr 2000). 

Huntington s disease (HD) is caused by mutations in a gene called Huntingtin. The disease is caused by abnormal expansion of CAG repeats, which encode long stretches of glutamine (polyglutamine). In addition to HD, there are several other known polyglutamine diseases such as spinocerebellar ataxia, and spinal and bulbar muscular atrophy. " ... 

The key symptoms of spinocerebellar ataxias (SCAs) include loss of balance, motor coordination, and malfunction of the cerebellum. There are several types of SCAs of which types 1, 2, 3, 6, 7, and 17 are... 

Table 1. CACNA1A (Ca 2.1, a 1A) Functional results for mutations associated with FHM = familial hemiplegic migraine, EA2 = episodic ataxia type 2, SCA6 = spinocerebellar ataxia type 6, PCA = progressive cerebellar ataxia (although addition mutations have been associated with these disorders, only those with reported functional data are listed)...

Figure 1. Mutations in the human Cnv 2.1 (P/Q-type) voltage-gated calcium channel associated with Familial Hemiplegic Migraine (FHM) and Spinocerebellar Ataxia Type-6 (SCA6)...

Ishikawa K, Fujigasaki H, Saegusa H, Ohwada K, Fujita T, Iwamoto H, Komatsuzaki Y, Torn S, Toriyama H, Watanabe M, Ohkoshi N, Shoji S, Kanazawa I, Tanabe T, Mizusawa H (1999) Abundant expression and cytoplasmic aggregations of [alpha] 1A voltage-dependent calcium channel protein associated with neurodegeneration in spinocerebellar ataxia type 6. Hum Mol Genet 8 1185-1193. 

Ishikawa K, Tanaka H, Saito M, Ohkoshi N, Fujita T, Yoshizawa K, Ikeuchi T, Watanabe M, Hayashi A, Takiyama Y, Nishizawa M, Nakano I, Matsubayashi K, Miwa M, Shoji S, Kanazawa I, Tsuji S, Mizusawa H (1997) Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19pl3.1-pl3.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19pl 3.1. Am J Hum Genet 61 336-346. 

Matsuyama Z, Wakamori M, Mori Y, Kawakami H, Nakamura S, Imoto K (1999) Direct alteration of the P/Q-type Ca2+ channel property by polyglutamine expansion in spinocerebellar ataxia 6. 

Piedras-Renteria ES, Watase K, Harata N, Zhuchenko O, Zoghbi HY, Lee CC, Tsien RW (2001) Increased expression of alpha 1A Ca2+ channel currents arising from expanded trinucleotide repeats in spinocerebellar ataxia type 6. J Neurosci 21 9185—9193. 

Restituito S, Thompson RM, Eliet J, Raike RS, Riedl M, Chamet P, Gomez CM (2000) The polyglutamine expansion in spinocerebellar ataxia type 6 causes a beta subunit-specific enhanced activation of P/Q-type calcium channels in Xenopus oocytes. J Neurosci 20 6394—6403. 

Torn S, Murakoshi T, Ishikawa K, Saegusa H, Fujigasaki H, Uchihara T, Nagayama S, Osanai M, Mizusawa H, Tanabe T (2000) Spinocerebellar ataxia type 6 mutation alters P-type calcium channel function. J Biol Chem 275 10893—10898. 

Koob MD, Moseley ML, Schut LJ, Benzow KA, Bird TD, Day JW, Ranum LP. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet 1999 21 379-384. 

DRPLA, dentatorubral-pallidoluysian atrophy SCA, spinocerebellar ataxia. 

Burk K, Globas C, Bosch S, Klockgether T, Ziihlke C, et al. 2003. Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3. J Neurol 250 207-211. 

Duenas AM, Goold R, Giunti P. 2006. Molecular pathogenesis of spinocerebellar ataxias. Brain 129 1357-1370. 

Joo EJ, Lee JH, Cannon TD, Price RA. 1999. Possible association between schizophrenia and a CAG repeat polymorphism in the spinocerebellar ataxia type 1 (SCA1) gene on human chromosome 6p23. Psychiatr Genet 9 7-11. 

Pujana MA, Martorell L, Volpini V, Valero J, Labad A, et al. 1997. Analysis of amino-acid and nucleotide variants in the spinocerebellar ataxia type 1 (SCA1) gene in schizophrenic patients. Hum Genet 99 772-775. 

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