第51回日本神経学会総会
＜シンポジウム16―5＞神経疾患とRNA
SCA31（脊髄小脳失調症31型）
石川 欽也1）, 佐藤 望1）, 新美 祐介1）, 網野 猛志1）2）, 水澤 英洋1）
1)東京医科歯科大学大学院脳神経病態学〔〒113―8519 東京都文京区湯島1―5―45〕
2)現 日本赤十字社武蔵野赤十字病院神経内科
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.
Full Text of this Article in Japanese PDF (338K)
(臨床神経, 50：985−987, 2010)
key words：SCA31，挿入変異，5塩基リピート，RNA
（受付日：2010年5月22日）
