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Molecular and clinical analyses of spinocerebellar ataxia type 8 in Japan

From the Department of Neurology, Gunma University School of Medicine, Maebashi, Japan.

Address correspondence and reprint requests to Dr. Yoshio Ikeda, Department of Neurology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Japan; e-mail: yikeda{at}akagi.sb.gunma-u.ac.jp

OBJECTIVE: To clarify the molecular and clinical features of the newly identified spinocerebellar ataxia type 8 (SCA8).

METHODS: We analyzed the CTG repeat region of the SCA8 gene in a series of Japanese patients with cerebellar ataxia. We also investigated the frequency of the CTG repeat length in Japanese normal elderly subjects older than age 79. Morphometric measurements on the cerebral MRI were compared between patients with SCA8 and SCA6.

RESULTS: The number of the combined CTA/CTG repeats of six affected SCA8 alleles was 106.3 ± 24.4 (mean ± SD) ranging from 89 to 155 and that of normal elderly subjects was 24.3 ± 4.4 (n = 104 alleles) ranging from 15 to 34. The mean age at onset of the SCA8 cases was 53.8 ± 19.7 years, with a range from 20 to 73 years. One father and daughter from an SCA8 family showed remarkable paternal anticipation. The number increase from father to daughter was +16 CTG repeats, with a 31-year acceleration of onset. The six identified SCA8 patients were clinically characterized by high frequencies of incoordination of trunk and limbs, ataxic dysarthria, impaired smooth pursuit, and horizontal nystagmus, and the MRI showed significant atrophy of the cerebellar vermis and hemispheres compared with that of normal controls. There was no significant difference between SCA8 and SCA6 on the morphometric MRI study.

CONCLUSIONS: The CTG repeat expansions in the SCA8 alleles were much greater than the range of repeats in normal elderly subjects. The SCA8 phenotype manifested by cerebellar symptoms and atrophy corresponded to features of the autosomal dominant cerebellar ataxia type III (ADCA III).

Key words: Spinocerebellar ataxia type 8—CTG repeat—Paternal anticipation—MRI morphometry—Myotonic dystrophy

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