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Spinocerebellar ataxia type 6: CAG repeat expansion in α 1a voltage‐dependent calcium channel gene and clinical variations in japanese population
Author(s) -
Ikeuchi Takeshi,
Takano Hiroki,
Koide Reiji,
Igarashi Shuichi,
Tanaka Hajime,
Tsuji Shoji,
Takahashi Hitoshi,
Horikawa Yoh,
Honma Yoshiaki,
Onishi Yoji,
Nakao Naoki,
Sahashi Ko,
Tsukagoshi Hiroshi,
Inoue Kiyoharu
Publication year - 1997
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/ana.410420609
Subject(s) - spinocerebellar ataxia , trinucleotide repeat expansion , ataxia , atrophy , degenerative disease , machado–joseph disease , population , age of onset , central nervous system disease , medicine , genetics , biology , disease , gene , neuroscience , allele , environmental health
Autosomal dominant spinocerebellar ataxias (SCAs) are clinically and genetically a heterogeneous group of neurodegenerative disorders. Recently, mild CAG repeat expansion in the α 1A voltage‐dependent calcium channel gene has been found to be associated with a type of autosomal dominant SCA (SCA6). We analyzed 98 Japanese families with autosomal dominant SCAs, for whom CAG repeat expansions of the SCA1, SCA2, Machado‐Joseph disease/SCA3, and dentatorubral‐pallidoluysian atrophy genes were excluded, and 5 apparently sporadic cases of cortical cerebellar atrophy. The diagnosis of SCA6 was confirmed in 30 families (31%) comprising 47 affected individuals and 1 sporadic case. The size of expanded CAG repeats ranged from 21 to 26 repeat units and was found to be correlated inversely with age at onset. We identified 2 SCA6 patients homozygous for expanded CAG repeats, whose ages at onset were earlier than the 95% lower confidence level, suggesting the presence of a gene dosage effect of expanded CAG repeat. Ataxia is the most common initial symptom found in 45 of the 48 patients. Patients with a prolonged disease course showed other accompanying clinical features including dystonic postures, involuntary movements, and abnormalities in tendon reflexes.