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Genetic screening of Greek patients with Huntington's disease phenocopies identifies an SCA8 expansion

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Abstract

Huntington’s disease (HD) is an autosomal dominant disorder characterized by a triad of chorea, psychiatric disturbance and cognitive decline. Around 1% of patients with HD-like symptoms lack the causative HD expansion and are considered HD phenocopies. Genetic diseases that can present as HD phenocopies include HD-like syndromes such as HDL1, HDL2 and HDL4 (SCA17), some spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA). In this study we screened a cohort of 21 Greek patients with HD phenocopy syndromes for mutations causing HDL2, SCA17, SCA1, SCA2, SCA3, SCA8, SCA12 and DRPLA. Fifteen patients (71%) had a positive family history. We identified one patient (4.8% of the total cohort) with an expansion of 81 combined CTA/CTG repeats at the SCA8 locus. This falls within what is believed to be the high-penetrance allele range. In addition to the classic HD triad, the patient had features of dystonia and oculomotor apraxia. There were no cases of HDL2, SCA17, SCA1, SCA2, SCA3, SCA12 or DRPLA. Given the controversy surrounding the SCA8 expansion, the present finding may be incidental. However, if pathogenic, it broadens the phenotype that may be associated with SCA8 expansions. The absence of any other mutations in our cohort is not surprising, given the low probability of reaching a genetic diagnosis in HD phenocopy patients.

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Acknowledgments

The work of MGS, NWW and HH was undertaken at UCLH/UCL, which received a proportion of the funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. NWW and HH are grateful to the MRC and Wellcome Trust for funding.

Conflicts of interest

The authors report no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK

    G. Koutsis, A. Pandraud, R. Paudel, H. Houlden & N. W. Wood

  2. Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, London, UK

    M. G. Sweeney

  3. Neurogenetics Unit, Department of Neurology, University of Athens Medical School, Eginitio Hospital, 74 Vas. Sophias Ave., 11528, Athens, Greece

    G. Koutsis, G. Karadima & M. Panas

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  1. G. Koutsis
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  2. G. Karadima
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  3. A. Pandraud
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  4. M. G. Sweeney
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  5. R. Paudel
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  6. H. Houlden
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  7. N. W. Wood
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  8. M. Panas
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Correspondence to G. Koutsis.

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Koutsis, G., Karadima, G., Pandraud, A. et al. Genetic screening of Greek patients with Huntington's disease phenocopies identifies an SCA8 expansion. J Neurol 259, 1874–1878 (2012). https://doi.org/10.1007/s00415-012-6430-9

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  • DOI: https://doi.org/10.1007/s00415-012-6430-9

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