Spinocerebellar ataxia type 31
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- Ishikawa Kinya
- Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University
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- Sato Nozomu
- Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University
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- Niimi Yusuke
- Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University
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- Amino Takeshi
- Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University Present Address: Department of Neurology, Musashino Red Cross Hospital
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- Mizusawa Hidehiro
- Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University
Bibliographic Information
- Other Title
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- シンポジウム１６‐５ 神経疾患とＲＮＡ ＳＣＡ３１（脊髄小脳失調症３１型）
Description
Spinocerebellar ataxia type 31 (SCA31) is a relatively common degenerative ataxia in Japan. We recently discovered SCA31 mutation as a complex pentanucleotide repeat containing (TAAAA)n, (TAGAA)n, and (TGGAA)n. The size of this repeat ranged from 2.8 to 3.5 kilo-base pairs (kb). Among these repeats, (TGGAA)n repeat appears crucial for SCA31 pathogenesis. The length of this complex repeat inversely correlated with ages of onset in patients. The mutation lies in an intron shared by two different genes, BEAN (brain expressed, associated with NEDD4) and TK2 (thymidine kinase 2), which are transcribed in opposite directions. Thus, the complex pentanucleotide sequence is predicted to be transcribed in both directions, but not necessarily translated into proteins. In situ hybridization analysis in patients' Purkinje cells demonstrated that pentanucleotide repeats transcribed in BEAN direction form RNA aggregates ("RNA foci"). We further found that splicing factors, SFRS1 and SFRS9, binds to (UGGAA)n, the transcript of (TGGAA)n in vitro. These findings may imply that SCA31 conforms to pathogenic mechanisms underlying non-coding repeat disorders, such as myotonic dystrophies (DM1 & DM2), and that SFRS1 and SFRS9 are involved in SCA31 pathogenesis.<br>
Journal
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- Rinsho Shinkeigaku
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Rinsho Shinkeigaku 50 (11), 985-987, 2010
Societas Neurologica Japonica
