Japanese amyotrophic lateral sclerosis patients with GGGGCC hexanucleotide repeat expansion in C9ORF72
- Takuya Konno1,
- Atsushi Shiga2,
- Akira Tsujino3,
- Akihiro Sugai1,
- Taisuke Kato1,
- Kazuaki Kanai4,
- Akio Yokoseki1,
- Hiroto Eguchi3,
- Satoshi Kuwabara4,
- Masatoyo Nishizawa1,
- Hitoshi Takahashi2,
- Osamu Onodera5
- 1Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
- 2Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
- 3First Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan
- 4Department of Neurology, Chiba University School of Medicine, Chiba, Japan
- 5Department of Molecular Neuroscience, Brain Research Institute, Niigata University, Niigata, Japan
- Correspondence to Dr Osamu Onodera, Department of Molecular Neuroscience, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuo-Ku, Niigata-City, Niigata 951-8585, Japan;
Contributors TK, AS, HT and OO contributed to the conception and design of the study. All the authors worked on the acquisition, analysis and interpretation of the data. TK, AS and OO drafted the manuscript. KK and HT assisted in writing and editing the manuscript.
- Received 13 January 2012
- Revised 9 July 2012
- Accepted 13 July 2012
- Published Online First 25 September 2012
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 (n=110) or control individuals (n=180) 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.
Funding Supported by Grant-in-Aid for Scientific Research (A) from Japan Society for the Promotion of Science, Grant-in-Aid for the Research Committee of CNS Degenerative Diseases from Ministry of Health, Labor and Welfare, Japan and Grant-in-Aid for the Nakabayashi Trust for ALS Research and a Grant-in-Aid for JSPS Fellows from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Competing interests None.
Ethics approval This study was conducted with the approval of the Niigata University Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.