SCA8 is an antisense transcript to the KLHL1 gene (homolog to the Drosophila KELCH gene); it does not itself appear to be protein coding. A cystine, thymine, guanine (CTG) trinucleotide repeat expansion that is incorporated into the SCA8 but not the KLHL1 transcript causes spinocerebellar ataxia type 8. When the CTG expansion is present, a polyglutamine mutant protein results.[2] Presumably the expansion interferes with normal antisense function of this transcript.[1]
↑Ikeda, Yoshio; Daughters, Randy S.; Ranum, Laura P. W. (2008). "Bidirectional expression of the SCA8 expansion mutation: one mutation, two genes". Cerebellum (London, England). 7 (2): 150–158. doi:10.1007/s12311-008-0010-7. ISSN1473-4230. PMID18418692.
Further reading
Koob MD, Moseley ML, Schut LJ, Benzow KA, Bird TD, Day JW, Ranum LP (Apr 1999). "An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8)". Nature Genetics. 21 (4): 379–84. doi:10.1038/7710. PMID10192387.
Nemes JP, Benzow KA, Moseley ML, Ranum LP, Koob MD (Jun 2000). "The SCA8 transcript is an antisense RNA to a brain-specific transcript encoding a novel actin-binding protein (KLHL1)". Human Molecular Genetics. 9 (10): 1543–51. doi:10.1093/hmg/9.10.1543. PMID10888605.
Jardim LB, Silveira I, Pereira ML, Ferro A, Alonso I, do Céu Moreira M, Mendonça P, Ferreirinha F, Sequeiros J, Giugliani R (Oct 2001). "A survey of spinocerebellar ataxia in South Brazil - 66 new cases with Machado-Joseph disease, SCA7, SCA8, or unidentified disease-causing mutations". Journal of Neurology. 248 (10): 870–6. doi:10.1007/s004150170072. PMID11697524.
Benzow KA, Koob MD (Mar 2002). "The KLHL1-antisense transcript ( KLHL1AS) is evolutionarily conserved". Mammalian Genome. 13 (3): 134–41. doi:10.1007/s00335-001-2105-2. PMID11919683.
Brusco A, Cagnoli C, Franco A, Dragone E, Nardacchione A, Grosso E, Mortara P, Mutani R, Migone N, Orsi L (Jul 2002). "Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1-3, 6 and 7 CAG expansions". Journal of Neurology. 249 (7): 923–9. doi:10.1007/s00415-002-0760-y. PMID12140678.
Andrés AM, Soldevila M, Saitou N, Volpini V, Calafell F, Bertranpetit J (Jan 2003). "Understanding the dynamics of Spinocerebellar Ataxia 8 (SCA8) locus through a comparative genetic approach in humans and apes". Neuroscience Letters. 336 (3): 143–6. doi:10.1016/S0304-3940(02)01249-1. PMID12505613.
Wu YR, Lin HY, Chen CM, Gwinn-Hardy K, Ro LS, Wang YC, Li SH, Hwang JC, Fang K, Hsieh-Li HM, Li ML, Tung LC, Su MT, Lu KT, Lee-Chen GJ (Mar 2004). "Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease". Clinical Genetics. 65 (3): 209–14. doi:10.1111/j.0009-9163.2004.00213.x. PMID14756671.
Sułek A, Hoffman-Zacharska D, Bednarska-Makaruk M, Szirkowiec W, Zaremba J (2004). "Polymorphism of trinucleotide repeats in non-translated regions of SCA8 and SCA12 genes: allele distribution in a Polish control group". Journal of Applied Genetics. 45 (1): 101–5. PMID14960773.
Factor SA, Qian J, Lava NS, Hubbard JD, Payami H (Mar 2005). "False-positive SCA8 gene test in a patient with pathologically proven multiple system atrophy". Annals of Neurology. 57 (3): 462–3. doi:10.1002/ana.20389. PMID15732096.
Moseley ML, Zu T, Ikeda Y, Gao W, Mosemiller AK, Daughters RS, Chen G, Weatherspoon MR, Clark HB, Ebner TJ, Day JW, Ranum LP (Jul 2006). "Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8". Nature Genetics. 38 (7): 758–69. doi:10.1038/ng1827. PMID16804541.
