Spinocerebellar ataxia type 8 (SCA8) is a rare autosomal dominant neurodegenerative disease caused by CTA/CTG repeat expansion in the ATXN8/ATXN8OS gene.
Out of 76 apparently homozygous subjects, RP-PCR allowed us to detect 56 expansions specific to DM2, and out of 378 ataxia patients, a large allele of the ATXN8OS gene (SCA8) was found in 25 subjects.
Spinocerebellar ataxia type 8 (SCA 8) is an autosomal dominant disorder characterized by cerebellar ataxia with additional features, such as upper motor neuron signs, urinary incontinence and dysphagia.
Bi-directional expression of the spinocerebellar ataxia type 8 (SCA8) CTG CAG expansion produces CUG expansion RNAs (CUG(exp)) from the ATXN8OS gene and a nearly pure polyglutamine expansion protein encoded by ATXN8 CAG(exp) transcripts expressed in the opposite direction.
Spinocerebellar ataxia 8 (SCA8), a triplet repeat expansion disorder, is genetically distinct from the other inherited ataxias, but its unusually variable phenotype can make its diagnosis difficult.
The objectives of this study were to: (i) establish whether the spinocerebellar ataxia type 8 (SCA 8) expansion is associated with ataxia in Scotland; (ii) test the hypothesis that SCA 8 is associated with neuropsychological impairment; and (iii) review neuroradiological findings in SCA 8.
Moreover, the expression of non-coding (CUG)(n) expansion transcripts (ataxin 8 opposite strand, ATXN8OS) and the discovery of intranuclear polyglutamine inclusions suggest SCA8 pathogenesis may involve toxic gain-of-function mechanisms at both the protein and RNA levels.
The size of the expansion was determined using a fluorescent PCR approach in 10 common SCA genes: SCA-1 (ATXN1), SCA-2 (ATXN2), SCA-3 (ATXN3), SCA-6 (CACNA1A), SCA-7 (ATXN7), SCA-8 (ATXN8OS), SCA-10 (ATXN10), SCA-12 (PPP2R2B), SCA-17 (TBP) and DRPLA (ATN1), in 165 ataxia patients and 307 controls of Welsh origin.
Moreover, the expression of noncoding (CUG)n expansion transcripts (ataxin 8 opposite strand, ATXN8OS) and the discovery of intranuclear polyglutamine inclusions suggests SCA8 pathogenesis involves toxic gain-of-function mechanisms at both the protein and RNA levels.
To establish whether the DNA expansion linked to spinocerebellar ataxia type 8 (SCA 8) is associated with ataxia in Scotland; to clarify the range of associated clinical phenotypes; and to compare the findings with previous reports.
Similarly, human KLHL1AS is expressed in various brain tissues, including the cerebellum, the tissue most affected by SCA8, and was detected at low levels in testis and kidney.