2012.12.11
Japanese amyotrophic lateral sclerosis patients with GGGGCC hexanucleotide repeat expansion in C9ORF72
Konno T1, Shiga A2, Tsujino A3, Sugai A1, Kato T1, Kanai K4, Yokoseki A1, Eguchi H3, Kuwabara S4, Nishizawa M1, Takahashi H2, Onodera O5.
1Department of Neurology, Brain Research Institute, Niigata University
2Department of Pathology, Brain Research Institute, Niigata University
3First Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Science, Nagasaki
4Department of Neurology, Chiba University School of Medicine, Chiba
5Department of Molecular Neuroscience, Brain Research Institute, Niigata University
Abstract
Background: A GGGGCC hexanucleotide repeat expansion in C9ORF72 occurs on a chromosome 9p21 locus that is linked with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in white populations. The diseases resulting from this expansion are referred to as 'c9FTD/ALS'. It has been suggested that c9FTD/ALS arose from a single founder. However, the existence of c9FTD/ALS in non-white populations has not been evaluated.
Results: We found two index familial ALS (FALS) patients with c9FTD/ALS in the Japanese population. The frequency of c9FTD/ALS was 3.4% (2/58 cases) in FALS. No patients with sporadic ALS (n¼110) or control individuals (n¼180) had the expansion. Neuropathological findings of an autopsy case were indistinguishable from those of white patients. Although the frequency of risk alleles identified in white subjects is low in Japanese, one patient had all 20 risk alleles and the other had all but one. The estimated haplotype indicated that the repeat expansion in these patients was located on the chromosome with the risk haplotype identified in white subjects.
Conclusions: C9ORF72 repeat expansions were present in a Japanese cohort of ALS patients, but they were rare. Intriguingly, Japanese patients appear to carry the same risk haplotype identified in white populations.
