Rinsho Shinkeigaku (Clinical Neurology)

The 51st Annual Meeting of the Japanese Society of Neurology

Spinocerebellar ataxia type 31

Kinya Ishikawa, M.D.1), Nozomu Sato, M.D.1), Yusuke Niimi, M.D.1), Takeshi Amino, M.D.1)2) and Hidehiro Mizusawa, M.D.1)

1)Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University
2)Present Address: Department of Neurology, Musashino Red Cross Hospital

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)

(CLINICA NEUROL, 50: 985|987, 2010)
key words: SCA31, insertion, pentanucleotide repeat, RNA

(Received: 22-May-10)