Genetic Creutzfeldt‒Jakob disease with 5-octapeptide repeats presented as frontotemporal dementia

Shinsuke Hamada; Ikuko Takahashi-Iwata; Katsuya Satoh; Tetsuyuki Kitamoto; Hidehiro Mizusawa; Fumio Moriwaka; Ichiro Yabe

doi:10.1038/s41439-023-00237-w

Genetic Creutzfeldt‒Jakob disease with 5-octapeptide repeats presented as frontotemporal dementia

Hum Genome Var. 2023 Mar 29;10(1):10. doi: 10.1038/s41439-023-00237-w.

Authors

Shinsuke Hamada^{1

2}, Ikuko Takahashi-Iwata¹, Katsuya Satoh³, Tetsuyuki Kitamoto⁴, Hidehiro Mizusawa⁵, Fumio Moriwaka², Ichiro Yabe⁶

Affiliations

¹ Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
² Hokkaido Neurology Hospital, Sapporo, Japan.
³ Department of Health Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
⁴ Department of Neurological Science, Tohoku University School of Medicine, Sendai, Japan.
⁵ National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
⁶ Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. yabe@med.hokudai.ac.jp.

Abstract

The N-terminus of the PRNP gene normally contains a 5-octapeptide repeat (R1-R2-R2-R3-R4), and insertions at this locus can cause hereditary prion diseases. In the present study, we found a 5-octapeptide repeat insertion (5-OPRI) in a sibling case of frontotemporal dementia. Consistent with previous literature, 5-OPRI rarely met the diagnostic criteria for Creutzfeldt‒Jakob disease (CJD). We propose 5-OPRI as a suspected causative mutation for early-onset dementia, especially the frontotemporal type.