わが国のALSにおけるC9ORF72

Abstract

Recently, C9orf72 hexanucleotide (GGGGCC) repeat expansion in intron 1 was reported to be the most common cause of sporadic and familial amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) in the Caucasian population. The frequency of the intronic repeat expansion is up to 21%-57% in familial ALS and 3%-21% in sporadic ALS.In the Japanese population, the C9orf72 repeat expansion was found to account for 2.8% (3/109) of familial ALS, 0.4% (4/891) of sporadic ALS, and 0% (0/377) of normal healthy controls. Notably, among the Kii peninsula which has recorded a high incidence of ALS or ALS/PDC (parkinsonism-dementia complex), the frequency of the C9orf72 repeat expansion was 20% (3/15) indicating a high prevalence. All patients with the repeat expansion had a common risk haplotype within a narrower region than the Finnish one, suggesting a common founder effect which spread from Europe to East Asia in human migration history.Although Japanese ALS patients with the C9orf72 repeat expansion were rarer than Caucasian patients, we should check family histories of other neurological disorders such as dementia and FTD and should do genetic testing more actively even in sporadic ALS patients. Further studies of C9orf72 will clarify the pathogenesis and find the treatments for familial and sporadic ALS (or ALS/FTD).