Analysis of C9orf72 repeat expansion in 563 Japanese patients with amyotrophic lateral sclerosis.
Recently, a hexanucleotide repeat expansion in C9orf72 was identified as the most common cause of both sporadic and familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Western populations. We analyzed 563 Japanese patients with ALS (552 sporadic and 11 familial) using fluorescent fragment-length analysis of C9orf72 and repeat-primed polymerase chain reaction analysis. Haplotype analysis was performed for 42 single nucleotide polymorphisms in patients with C9orf72 repeat expansion. C9orf72 repeat expansion was found in 2 patients with sporadic ALS (2/552 = 0.4%) and no patients with familial ALS (0/11 = 0%). In the probands' families, 1 primary progressive aphasia patient and 1 asymptomatic 76-year-old individual exhibited C9orf72 repeat expansion. All of the patients with the C9orf72 repeat expansion carried the 20-single nucleotide polymorphism consensus risk haplotype. The frequency of the C9orf72 repeat expansion among Japanese patients is much lower than in Western populations. The existence of a 76-year-old asymptomatic carrier supported the notion of incomplete penetrance. The C9orf72 mutation should be analyzed in sporadic ALS patients after determining their family histories not only of frontotemporal dementia but also of primary progressive aphasia.
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Kotaro
K
Ogaki
Yuanzhe
Y
Li
Naoki
N
Atsuta
Hiroyuki
H
Tomiyama
Manabu
M
Funayama
Hazuki
H
Watanabe
Ryoichi
R
Nakamura
Hideo
H
Yoshino
Seiji
S
Yato
Asako
A
Tamura
Yutaka
Y
Naito
Akira
A
Taniguchi
Koji
K
Fujita
Yuishin
Y
Izumi
Ryuji
R
Kaji
Nobutaka
N
Hattori
Gen
G
Sobue
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D000073885:C9orf72 Protein; D042622:DNA Repeat Expansion / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins