Accumulation Area of a Japanese PRNP P102L Variant Associated With Gerstmann–Sträussler–Scheinker Disease: The Ariake PRNP P102L Variant
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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-Kresistant 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.
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-Kresistant 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.
참고문헌 (35)
- Kim MO, "Genetic PrP prion diseases", Cold Spring Harb Perspect Biol, 10, pp.a033134~ (2018)
- Hsiao K, "Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome", Nature, 338, pp.342~345 (1989)
- Kitamoto T, "A new inherited prion disease(PrP-P105L mutation)showing spastic paraparesis", Ann Neurol, 34, pp.808~813 (1993)
- Kovács GG, "Inherited prion disease with A117V mutation of the prion protein gene : a novel Hungarian family", J Neurol Neurosurg Psychiatry, 70, pp.802~805 (2001)
- Dlouhy SR, "Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene", Nat Genet, 1, pp.64~67 (1992)
- Baiardi S, "Gerstmann-Sträussler-Scheinker disease(PRNP p. D202N)presenting with atypical parkinsonism", Neurol Genet, 6, pp.e400~ (2020)
- Yamada M, "Involvement of the spinal posterior horn in Gerstmann-Sträussler-Scheinker disease(PrP P102L)", Neurology, 52, pp.260~265 (1999)
- Jiang AA, "Gerstmann-Sträussler-Scheinker syndrome misdiagnosed as conversion disorder", BMJ Case Rep, 12, pp.e229729~ (2019)
- Tesar A, "Clinical variability in P102L Gerstmann-Sträussler-Scheinker syndrome", Ann Neurol, 86, pp.643~652 (2019)
- Higuma M, "Relationships between clinicopathological features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases", PLoS One, 8, pp.e60003~ (2013)
- Kitamoto T, "Novel missense variants of prion protein in Creutzfeldt-Jakob disease or Gerstmann-Sträussler syndrome", Biochem Biophys Res Commun, 191, pp.709~714 (1993)
- Honda H, "Frequent detection of pituitary-derived PrPres in human prion diseases", J Neuropathol Exp Neurol, 78, pp.922~929 (2019)
- Nozaki I, "Prospective 10-year surveillance of human prion diseases in Japan", Brain, 133, pp.3043~3057 (2010)
- Krasnianski A, "Clinical findings and diagnosis in genetic prion diseases in Germany", Eur J Epidemiol, 31, pp.187~196 (2016)
- Liberski PP, "Gerstmann-Sträussler-Scheinker disease", Adv Exp Med Biol, 724, pp.128~137 (2012)
- Wang J, "Analysis of 12 Chinese patients with proline-to-leucine mutation at codon 102-associated Gerstmann-Sträussler-Scheinker disease", J Clin Neurol, 15, pp.184~190 (2019)
- Wieser HG, "EEG in Creutzfeldt-Jakob disease", Clin Neurophysiol, 117, pp.935~951 (2006)
- Pascuzzo R, "Prion propagation estimated from brain diffusion MRI is subtype dependent in sporadic Creutzfeldt-Jakob disease", Acta Neuropathol, 140, pp.169~181 (2020)
- Parchi P, "Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects", Ann Neurol, 46, pp.224~233 (1999)
- Hoshi H, "Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis", J Bone Miner Res, 27, pp.2015~2023 (2012)
- Riudavets MA, "Gerstmann-Sträussler-Scheinker syndrome with variable phenotype in a new kindred with PRNP-P102L mutation", Brain Pathol, 24, pp.142~147 (2014)
- Umeh CC, "Clinicopathological correlates in a PRNP P102L mutation carrier with rapidly progressing parkinsonism-dystonia", Mov Disord Clin Pract, 3, pp.355~358 (2016)
- Honda H, "Different complicated brain pathologies in monozygotic twins with Gerstmann-Sträussler-Scheinker disease", J Neuropathol Exp Neurol, 76, pp.854~863 (2017)
- Webb TE, "Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series", Brain, 131(Pt 10), pp.2632~2646 (2008)
- Barbanti P, "Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Sträussler-Scheinker disease(PrP-P102L mutation)", Neurology, 47, pp.734~741 (1996)
- Bugiani O, "Neuropathology of Gerstmann-Sträussler-Scheinker disease", Microsc Res Tech, 50, pp.10~15 (2000)
- Parchi P, "Genetic influence on the structural variations of the abnormal prion protein", Proc Natl Acad Sci U S A, 97, pp.10168~10172 (2000)
- Colucci M, "Gerstmann-Sträussler-Scheinker : a new phenotype with ‘curly’ PrP deposits", J Neuropathol Exp Neurol, 65, pp.642~651 (2006)
- Nonno R, "Transmissibility of Gerstmann-Sträussler-Scheinker syndrome in rodent models : new insights into the molecular underpinnings of prion infectivity", Prion, 10, pp.421~433 (2016)
- Appleby BS, "Genetic aspects of human prion diseases", Front Neurol, 13, pp.1003056~ (2022)
- White MD, "Therapy for prion diseases : insights from the use of RNA interference", Prion, 3, pp.121~128 (2009)
- Minikel EV, "Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints", Nucleic Acids Res, 48, pp.10615~10631 (2020)
- Raymond GJ, "Antisense oligonucleotides extend survival of prion-infected mice", JCI Insight, 5, pp.e131175~ (2019)
- Gu H, "IVIG delays onset in a mouse model of Gerstmann-Sträussler-Scheinker disease", Mol Neurobiol, 56, pp.2353~2361 (2019)
- Minikel EV, "Age at onset in genetic prion disease and the design of preventive clinical trials", Neurology, 93, pp.e125~e134 (2019)