＜教育講演（1）―5＞
ALSの遺伝学Update
青木 正志, 割田 仁, 鈴木 直輝, 加藤 昌昭
東北大学大学院医学系研究科神経内科，東北大学病院ALS 治療・開発センター〔〒980―8574 仙台市青葉区星陵町1―1〕
Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disorder characterized by the death of upper and lower motor neurons. In familial ALS kinders with mutations in the SOD1 gene, the age of onset of weakness varies greatly but the duration of illness appears to be characteristic to each mutation. Mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene have been discovered to be associated with familial ALS. In a Japanese family with familial ALS, we found the R521C FUS mutation, which has been reported to be found in various ethnic backgrounds. The family history revealed 23 patients with ALS among 46 family members, suggesting a 100% penetrance rate. They developed muscle weakness at an average age of 35.3 years, and the average age of death was 37.2 years. Neuropathological examination revealed remarkable atrophy of the brainstem tegmentum characterized by cytoplasmic basophilic inclusion bodies in the neurons of the brainstem. The frequency of a hexanucleotide repeat expansion in C9ORF72 with familial ALS has been estimated as approximately 5% in Japan, although the one Japanese patient was identified as a carrier of the C9ORF72 expansion carried the Finnish risk haplotype.
Full Text of this Article in Japanese PDF (703K)
(臨床神経, 52：844−847, 2012)
key words：筋萎縮性側索硬化症，C9ORF72，SOD1，FUS/TLS，遺伝子変異
（受付日：2012年5月23日）
