Accumulation Area of a Japanese PRNP P102L Variant: The Ariake PRNP P102L Variant

Kohei Suzuyama; Makoto Eriguchi; Hiromu Minagawa; Hiroyuki Honda; Keita Kai; Tetsuyuki Kitamoto; Hideo Hara

doi:10.3988/jcn.2023.0102

Accumulation Area of a Japanese PRNP P102L Variant: The Ariake PRNP P102L Variant

J Clin Neurol. 2024 Jan 1. doi: 10.3988/jcn.2023.0102. Online ahead of print.

Authors

Kohei Suzuyama¹, Makoto Eriguchi², Hiromu Minagawa², Hiroyuki Honda^{3

4}, Keita Kai⁵, Tetsuyuki Kitamoto⁶, Hideo Hara²

Affiliations

¹ Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan. sj8817@cc.saga-u.ac.jp.
² Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan.
³ Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁴ Department of Neurology, Neuro Muscular Center, National Hospital Organization Omuta National Hospital, Omuta, Japan.
⁵ Department of Pathology, Saga University Hospital, Saga, Japan.
⁶ Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.

PMID: 38171504
DOI: 10.3988/jcn.2023.0102

Abstract

Background and purpose: The coast of Kyushu Island on Ariake Sea in Japan is known to be an accumulation area for patients with a proline-to-leucine substitution mutation at residue 102 (P102L) of the human prion protein gene (PRNP), which is associated with Gerstmann-Sträussler-Scheinker disease. We designated this geographical distribution as the "Ariake PRNP P102L variant." The purpose of this study was to characterize the clinical features of this variant.

Methods: We enrolled patients with the PRNP P102L variant who were followed up at the Saga University Hospital from April 2002 to November 2019. The clinical information of patients were obtained from medical records, including clinical histories, brain magnetic resonance imaging (MRI), and electroencephalography (EEG). A brain autopsy was performed on one of the participants.

Results: We enrolled 24 patients from 19 family lines, including 12 males. The mean age at symptom onset was 60.6 years (range, 41-77 years). The incidence rate of the Ariake PRNP P102L variant was 3.32/1,000,000 people per year in Saga city. The initial symptoms were ataxia (ataxic gait or dysarthria) in 19 patients (79.2%), cognitive impairment in 3 (12.5%), and leg paresthesia in 2 (8.3%). The median survival time from symptom onset among the 18 fatal cases was 63 months (range, 23-105 months). Brain MRI revealed no localized cerebellar atrophy, but sparse diffusion-weighted imaging abnormalities were detected in 16.7% of the patients. No periodic sharp-wave complexes were identified in EEG. Neuropathological investigations revealed uni- and multicentric prion protein (PrP) plaques in the cerebral cortex, putamen, thalamus, and cerebellum of one patient. Western blot analysis revealed 8-kDa proteinase-K-resistant PrP.

Conclusions: This is the first report of the accumulation area of a PRNP P102L variant on the coast of Ariake Sea. The Ariake PRNP P102L variant can be characterized by a relatively long disease duration with sparse abnormalities in brain MRI and EEG relative to previous reports. Detailed interviews to obtain information on the birthplace and the family history of related symptoms are important to diagnosing a PRNP P102L variant.

Keywords: Gerstmann–Sträussler–Scheinker disease; P102L; genetic prion.