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Clinical and genetic findings in Finnish ataxia patients with the spinocerebellar ataxia 8 repeat expansion
Author(s) -
Juvonen Vesa,
Hietala Marja,
Päivärinta Markku,
Rantamäki Maria,
Hakamies Lauri,
Kaakkola Seppo,
Vierimaa Outi,
Penttinen Maila,
Savontaus MarjaLiisa
Publication year - 2000
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(200009)48:3<354::aid-ana10>3.0.co;2-a
Subject(s) - spinocerebellar ataxia , trinucleotide repeat expansion , ataxia , penetrance , apraxia , medicine , genetics , psychology , biology , neuroscience , allele , gene , phenotype , aphasia
Abstract Spinocerebellar ataxia 8 (SCA8) is caused by a CTG repeat expansion in an untranslated region of a recently cloned gene on 13q21. The pathogenic role of this trinucleotide repeat was evaluated by examining 154 Finnish ataxia patients and 448 controls. Expansions ranging from 100 to 675 repeats were present in 9 (6%) unrelated patients and in 13 (3%) controls. There was a threefold excess of shorter expansions (<204 repeats) in the ataxia series, and the expansions tended to cluster in patients with a family history for the disease. Clinical and genetic data were subsequently collected from 15 patients. Common initial symptoms included gait instability, dysarthria, and tremor. A marked cerebellar atrophy in magnetic resonance imaging or computed tomography was found in all patients. Pyramidal affection was often seen, and various kinds of cognitive impairment were evident in 40% of patients. Disease progression was slow, and fluctuation of symptoms was commonly observed. A maternal penetrance bias was not seen, nor was there any clear‐cut negative correlation between age of onset and repeat number. Meiotic but not mitotic instability of the repeat expansion was evident. Haplotype analysis suggests multiple origins for the Finnish spinocerebellar ataxia 8 repeat expansions. Ann Neurol 2000;48:354–361