Details

Autor(en) / Beteiligte

• Soga, Kazumasa
• Ishikawa, Kinya
• Furuya, Tokuro
• Iida, Tadatsune
• Yamada, Tetsuo
• Ando, Noboru
• Ota, Kiyobumi
• Kanno-Okada, Hiromi
• Tanaka, Shinya
• Shintaku, Masayuki
• Eishi, Yoshinobu
• Mizusawa, Hidehiro
• Yokota, Takanori

Titel

Gene dosage effect in spinocerebellar ataxia type 6 homozygotes: A clinical and neuropathological study

Ist Teil von

• Journal of the neurological sciences, 2017-02, Vol.373, p.321-328

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disorder. However, it remains unclear whether SCA6 shows a gene dosage effect, defined by earlier age-of-onset in homozygotes than heterozygotes. Herein, we retrospectively analyzed four homozygous SCA6 subjects from our single institution cohort of 120 SCA6 subjects. We also performed a neuropathological investigation into an SCA6 individual with compound heterozygous expansions. In the 116 heterozygotes, there was an inverse correlation of age-of-onset with the number of CAG repeats in the expanded allele, and with the total number of CAG repeats, in both normal and expanded alleles. The age-of-onset in the four homozygotes was within the 95% confidence interval of the age-of-onset versus the repeat-lengths correlations determined in the 116 heterozygotes. Nevertheless, all homozygotes had earlier onset than their parents, and showed rapid disease progression. Neuropathology revealed neuronal loss, as well as α1A-calcium channel protein aggregates in Purkinje cells, a few α1A-calcium channel protein aggregates in the neocortex and basal ganglia, and neuronal loss in Clarke ' s column and the globus pallidus not seen in heterozygotes. These data suggest a mild clinical and neuropathological gene dosage effect in SCA6 subjects.