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Large, expanded repeats in SCA8 are not confined to patients with cerebellar ataxia

Nature Genetics volume 24, pages 214–215 (2000)Cite this article

The spinocerebellar ataxia 8 gene (SCA8) was recently cloned from the genomic DNA of an ataxia patient by means of the RAPID technique1. Koob et al. demonstrated linkage of an expanded CTA/CTG repeat in SCA8 to the disease phenotype in a large family with cerebellar ataxia. Alleles of affected individuals contained 110–130 combined CTA/CTG repeats (CRs), whereas alleles in 1,200 control chromosomes contained 16–92 CRs. Eight other ataxia families that were too small for linkage analysis were shown to harbour expanded SCA8 alleles with approximately 90–250 CRs; these were termed ‘potentially pathogenic’ alleles. Thus, distinct normal and pathological ranges could not be determined.

We screened 98 unrelated cases of autosomal dominant cerebellar ataxia (ADCA), 145 cases of idiopathic late onset cerebellar ataxia (ILOCA) and 21 unrelated individuals with suspected autosomal recessive cerebellar ataxia (ARCA). All were negative for expansions in the known SCA genes and the Friedreich ataxia gene. In addition, to establish the specificity of the SCA8 test, we genotyped 1,306 control chromosomes from sources including DNA extracted from neuropathologically normal brain and from individuals with unrelated diseases such as hereditary motor and sensory neuropathy (HMSN) and neuropathologically proven idiopathic Parkinson disease (IPD). We used 5′-fluorescent F4 and R4 primers as described1 to amplify the SCA8 expansion. We sequenced expanded alleles with more than or equal to 100 CRs to determine CTA/CTG configuration.

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Figure 1: Size distribution of combined CTA/CTG repeats among control chromosomes (n=1306).
Figure 2: Genealogical tree of patient 2.

References

  1. Koob, M.D. et al. Nature Genet. 21, 379–384 (1999).

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  2. Harding, A.E., Diengdoh, J.V. & Lees, A.J. J. Neurol. Neurosurg. Psychiatry 47, 853–856 (1984).

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Acknowledgements

We thank the subjects for their participation. DNA from IPD brains and clinical information from IPD patients was provided by The Parkinson's Disease Society Brain Research Centre. DNA from brains of normal control subjects was provided by C. Morris of the Medical Research Council Neurochemical Pathology Unit. DNA from IPD and control brains was also provided by The Alzheimer's Brain Bank.

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  1. Department of Clinical Neurology, Neurogenetics Section, Institute of Neurology, Queen Square, London, UK

    Paul F. Worth, Henry Houlden, Paola Giunti, Mary B. Davis & Nicholas W. Wood

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  1. Paul F. Worth
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  2. Henry Houlden
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  3. Paola Giunti
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Correspondence to Mary B. Davis.

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Worth, P., Houlden, H., Giunti, P. et al. Large, expanded repeats in SCA8 are not confined to patients with cerebellar ataxia. Nat Genet 24, 214–215 (2000). https://doi.org/10.1038/73411

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