Biochemical features of genetic Creutzfeldt-Jakob disease with valine-to-isoleucine substitution at codon 180 on the prion protein gene

Ito, Yoko; Sanjo, Nobuo; Hizume, Masaki; Kobayashi, Atsushi; Ohgami, Tatsuhiro; Satoh, Katsuya; Hamaguchi, Tetsuya; Yamada, Masahito; Kitamoto, Tetsuyuki; Mizusawa, Hidehiro; Yokota, Takanori

doi:10.1016/j.bbrc.2018.01.119

Cited by 5 publications

(19 citation statements)

References 32 publications

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“…However, we regard 180 Val/Ile and 252 Met/Arg as major variants because the number of patients carrying these variants is increasing in Japan 13. We assume 180 Val/Ile to be a causative mutation despite its low penetrance because several studies previously reported it to be associated with a characteristic and uniform disease phenotype, which differs from that of other human prion diseases such as sporadic CJD 38 39. By contrast, although M232R may be a potential risk variant, no studies have indicated it to be a causative mutation.…”

Section: Discussionmentioning

confidence: 99%

Methionine homozygosity for PRNP polymorphism and susceptibility to human prion diseases

Kosami

Hamaguchi

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundNo studies have assessed the independent association of methionine homozygosity at codon 129 with the susceptibility to prion diseases, controlling for the effects of the codon 219 polymorphisms and other potential confounders, using a large-scale population-based dataset.MethodsWe conducted a case-control study using a Japanese nationwide surveillance database for prion diseases. The main exposure was methionine homozygosity at codon 129, and the outcome was development of prion diseases. Multivariable logistic regression models were employed for specific disease subtypes (sporadic Creutzfeldt-Jakob disease (CJD), genetic CJD and Gerstmann-Sträussler-Scheinker disease (GSS)).ResultsOf 5461 patients registered in the database, 2440 cases and 796 controls remained for the analysis. The cases comprised 1676 patients with sporadic CJD (69%), 649 with genetic CJD (27%) and 115 with GSS (5%). For patients with methionine homozygosity, potential risk for occurring prion diseases: adjusted OR (95% CI) was 2.21 (1.46 to 3.34) in sporadic CJD, 0.47 (0.32 to 0.68) in genetic CJD and 0.3 (0.17 to 0.55) in GSS. Among patients with specific prion protein abnormalities, the potential risk was 0.27 (0.17 to 0.41) in genetic CJD with 180 Val/Ile, 1.66 (0.65 to 5.58) in genetic CJD with 200 Glu/Lys, 3.97 (1.2 to 24.62) in genetic CJD with 232 Met/Arg and 0.71 (0.34 to 1.67) in GSS with 102 Pro/Leu.ConclusionsMethionine homozygosity at codon 129 was predisposing to sporadic CJD, but protective against genetic CJD and GSS, after adjustment for codon 219 polymorphism effect. However, the impacts differed completely among patients with specific prion protein abnormalities.

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Section: Discussionmentioning

confidence: 99%

Methionine homozygosity for PRNP polymorphism and susceptibility to human prion diseases

Kosami

Hamaguchi

et al. 2022

J Neurol Neurosurg Psychiatry

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“…Further studies are needed to better understand the overall mechanisms of the disease in carriers of the rare 180I-129V haplotype. The origin of the mutation may be investigated by NGS sequencing of exon 2 in the PRNP gene to identify specific haplotypes [ 26 ]; an estimate of V180I penetrance in rare diseases is possible only through collaboration with the European surveillance network in order to include as many cases as possible with accurate clinical and laboratory data. Finally, it is important to determine whether this rare form of gCJD is transmissible to laboratory animals.…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene

Zanusso

Colaizzo

Poleggi

et al. 2022

IJMS

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Genetic Creutzfeldt–Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (PRNP) in phase with residue 129M is the most frequent cause of gCJD in East Asia, whereas it is quite uncommon in Caucasians. We report on a gCJD patient with the rare V180I-129V haplotype, showing an unusually long duration of the disease and a characteristic pathological PrP (PrPSc) glycotype. Family members carrying the mutation were fully asymptomatic, as commonly observed with this mutation. Neuropathological examination showed a lesion pattern corresponding to that commonly reported in Japanese V180I cases with vacuolization and gliosis of the cerebral cortexes, olfactory areas, hippocampus and amygdala. PrP was deposited with a punctate, synaptic-like pattern in the cerebral cortex, amygdala and olfactory tract. Western blot analyses of proteinase-K-resistant PrP showed the characteristic two-banding pattern of V180I gCJD, composed of mono- and un-glycosylated isoforms. In line with reports on other V180I cases in the literature, Real-Time Quaking Induced Conversion (RT-QuIC) analyses did not demonstrate the presence of seeding activity in the cerebrospinal fluid and olfactory mucosa, suggesting that this haplotype also may result in a reduced seeding efficiency of the pathological PrP. Further studies are required to understand the origin, penetrance, disease phenotype and transmissibility of 180I-129V haplotype in Caucasians.

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“…From these reports, CSF or EEG analysis has an inferior sensitivity for detecting asymptomatic CJD pathogenesis compared to DWI. In particular, CJD patients with the V180I mutation have low rates of positivity for t-tau protein, 14-3-3 protein, RT-QuIC, and PSWC, even after symptom onset (16). In addition, CSF analysis is rarely performed before CJD is suspected because of its invasiveness.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Extremely Early Detection of Preclinical Magnetic Resonance Imaging Abnormality in Creutzfeldt–Jakob Disease With the V180I Mutation

et al. 2021

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The diagnosis of presymptomatic Creutzfeldt–Jakob disease (CJD) is challenging. The levels of total tau protein, 14-3-3 protein, and protease-resistant isoform of prion protein (PrPres) in the cerebrospinal fluid; periodic sharp wave complexes on electroencephalography; and diffusion-weighted imaging (DWI) of brain magnetic resonance imaging (MRI) have all been used to diagnose symptomatic CJD, but none of these markers have been established in the diagnosis of presymptomatic CJD. Here, we report a case of genetic CJD with the V180I mutation in which a small punctate cortical hyperintensity was detected on DWI 6 months before symptom onset and 9 months before diagnosis. Presymptomatic CJD is currently impossible to diagnose because of the lack of established early diagnostic markers. However, since MRI is increasingly used in daily clinical practice, the chance detection of such DWI abnormalities would have important implications in terms of providing a clue to examine a highly specific early diagnostic marker to be developed in the future for CJD. This will allow presymptomatic intervention by disease-modifying therapy in the near future.

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Biochemical features of genetic Creutzfeldt-Jakob disease with valine-to-isoleucine substitution at codon 180 on the prion protein gene

Cited by 5 publications

References 32 publications

Methionine homozygosity for PRNP polymorphism and susceptibility to human prion diseases

Methionine homozygosity for PRNP polymorphism and susceptibility to human prion diseases

Biochemical and Neuropathological Findings in a Creutzfeldt–Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene

Case Report: Extremely Early Detection of Preclinical Magnetic Resonance Imaging Abnormality in Creutzfeldt–Jakob Disease With the V180I Mutation

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