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.
- Amyotrophic lateral sclerosis
- DNA repeat expansion
- chromosome 9
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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.