第50回日本神経学会総会
＜シンポジウム9―1＞ポリグルタミン病への分子生物学的アプローチ
脊髄小脳変性症への分子遺伝学的アプローチ
石川 欽也, 石黒 太郎, 高橋 真, 佐藤 望, 網野 猛志, 新美 祐介, 水澤 英洋
東京医科歯科大学大学院医歯学総合研究科脳神経病態学分野〔〒113-8519 東京都文京区湯島1-5-45〕
Spinocerebellar ataxia (SCA) is a group of degenerative ataxias with autosomal dominant inheritance. The most common form of mutation that causes SCA is the expansion of trinucleotide (CAG) repeat encoding polyglutamine. These "polyglutamine disorders" are, SCA1, SCA2, Machado-Joseph disease, SCA6, SCA7, SCA17 and DRPLA. Another dynamic mutation, yet a non-coding one, has been identified as the cause of SCA8, SCA10 and SCA12. This mutation includes, trinucleotide (CAG/CTG) expansion causing SCA8 and SCA12, and pentanuclotide (ATTCT) expansion leading SCA10. In addition to these dynamic mutations, static mutations, such as missense mutations and deletions, have been identified to cause SCA5, SCA11, SCA13, SCA14, SCA15 and SCA27.
Since 1992, authors have been involved in identifying the mutation (s) of autosomal dominant cerebellar ataxia with rather pure cerebellar syndrome (ADCAIII). About a half of our cohort with ADCAIII were SCA6, caused by a small CAG repeat expansion in the α1A-voltage-dependent calcium channel gene. Recent study in patients' brains suggested that a small polyglutamine expansion leads a portion of this channel protein to aggregate in the Purkinje cell. Another type of ADCAIII is the chromosome 16q22.1-linked ADCA. By a comprehensive positional cloning strategy, we have found a genetic change that segregate with the disease. Identifying the mutation of 16q-ADCA is imperative for understanding molecular basis of this disease.
Full Text of this Article in Japanese PDF (455K)
(臨床神経, 49：907−909, 2009)
key words：脊髄小脳変性症, 脊髄小脳失調症, ポジショナルクローニング, 遺伝子変異
（受付日：2009年5月22日）
