scholarly journals Genetic Risk Factors of Creutzfeldt-Jakob Disease in the Population of Newborns in Slovakia

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 435
Author(s):  
Dana Kosorinova ◽  
Girma Belay ◽  
Dana Zakova ◽  
Martin Stelzer ◽  
Eva Mitrova
Keyword(s):  
Genetic Testing ◽  
Protein Gene ◽  
Risk Group ◽  
Prnp Gene ◽  
Human Prion Disease ◽  
E200k Mutation ◽  
Jakob Disease ◽  
Pcr Method ◽  
Asymptomatic Phase ◽  
Genetic Form

The most frequent human prion disease is Creutzfeldt–Jakob disease (CJD). It occurs as sporadic (sCJD), genetic (gCJD), iatrogenic (iCJD) form and as variant CJD. The genetic form represents about 10–15% of confirmed cases worldwide, in Slovakia as much as 65–75%. Focal accumulation of gCJD was confirmed in Orava region. The most common point mutation of the prion protein gene (PRNP) is E200K. CJD has a long asymptomatic phase and it is not known when the carriers of the mutation E200K become infectious. Precautions to prevent iCJD are focused especially on clinical CJD cases, but asymptomatic CJD-specific mutation carriers cannot be excluded, and represent a potential genetic CJD-risk group. The aim of this study was to determine the occurrence, frequency and geographic distribution of the E200K mutation among the newborns, comparing the areas of focal accumulation of gCJD with extra-focal ones, as well as distribution of the polymorphism M129V of the PRNP gene. A total of 2915 samples of dry blood spots from anonymous newborns were analyzed. We used RealTime PCR method to determine the presence of the E200K mutation and the M129V polymorphism. Genetic testing revealed 13 carriers of the E200K mutation. Investigation of the M129V polymorphism affirmed higher representation of methionine homozygotes (48% MM, 44% MV, 8% VV). Achieved results fully confirmed our previous observations concerning both the specific and nonspecific genetic CJD risk among the Slovak general population. The 48% of methionine homozygotes and 4 carriers of the E200K mutation among 1000 live-born children in Slovakia underline the benefits of genetic testing.

scholarly journals The First Meta-Analysis of the M129V Single-Nucleotide Polymorphism (SNP) of the Prion Protein Gene (PRNP) with Sporadic Creutzfeldt–Jakob Disease

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3132
Author(s):  
Yong-Chan Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Meta Analysis ◽  
Prnp Gene ◽  
Case Control ◽  
Prion Protein Gene ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Jakob Disease ◽  
Sporadic Cjd

Prion diseases are fatal, chronic, and incurable neurodegenerative diseases caused by pathogenic forms of prion protein (PrPSc) derived from endogenous forms of prion protein (PrPC). Several case–control and genome-wide association studies have reported that the M129V polymorphism of the human prion protein gene (PRNP) is significantly associated with susceptibility to sporadic Creutzfeldt–Jakob disease (CJD). However, since some case–control studies have not shown these associations, the results remain controversial. We collected data that contain the genotype and allele frequencies of the M129V single-nucleotide polymorphism (SNP) of the PRNP gene and information on ethnic backgrounds from sporadic CJD patients. We performed a meta-analysis by collecting data from eligible studies to evaluate the association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD. We found a very strong association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD using a meta-analysis for the first time. We validated the eligibility of existing reports and found severe heterogeneity in some previous studies. We also found that the MM homozygote is a potent risk factor for sporadic CJD compared to the MV heterozygote in the heterozygote comparison model (MM vs. MV, odds ratio = 4.9611, 95% confidence interval: 3.4785; 7.0758, p < 1 × 10−10). To the best of our knowledge, this was the first meta-analysis assessment of the relationship between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD.

scholarly journals Complete Penetrance of Creutzfeldt-Jakob Disease in Libyan Jews Carrying the E200K Mutation in the Prion Protein Gene

1995 ◽  
Vol 1 (6) ◽  
pp. 607-613 ◽  
Author(s):  
Serena Spudich ◽  
James A. Mastrianni ◽  
Margaret Wrensch ◽  
Ruth Gabizon ◽  
Zeev Meiner ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Prion Protein Gene ◽  
Complete Penetrance ◽  
E200k Mutation ◽  
Jakob Disease

scholarly journals Age at Death of Creutzfeldt-Jakob Disease in Subsequent Family Generation Carrying the E200K Mutation of the Prion Protein Gene

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e60376 ◽  
Author(s):  
Maurizio Pocchiari ◽  
Anna Poleggi ◽  
Maria Puopolo ◽  
Marco D’Alessandro ◽  
Dorina Tiple ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Prion Protein Gene ◽  
Age At Death ◽  
E200k Mutation ◽  
Jakob Disease ◽  
Family Generation

A novel phenotype in familial Creutzfeldt-Jakob disease: Prion protein gene E200K mutation coupled with valine at codon 129 and type 2 protease-resistant prion protein

1999 ◽  
Vol 45 (6) ◽  
pp. 812-816 ◽  
Author(s):  
Johannes A. Hainfellner ◽  
Piero Parchi ◽  
Tetsuyuki Kitamoto ◽  
Christa Jarius ◽  
Pierluigi Gambetti ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Prion Protein Gene ◽  
E200k Mutation ◽  
Jakob Disease ◽  
Codon 129

scholarly journals The First Report of the Prion Protein Gene (PRNP) Sequence in Pekin Ducks (Anas platyrhynchos domestica): The Potential Prion Disease Susceptibility in Ducks

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 193
Author(s):  
Min-Ju Jeong ◽  
Yong-Chan Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Prion Protein ◽  
Dna Sequence ◽  
Prion Disease ◽  
Protein Gene ◽  
Prnp Gene ◽  
Pekin Duck ◽  
Prion Protein Gene ◽  
First Report ◽  
Aggregation Propensity ◽  
Pekin Ducks

Pathogenic prion protein (PrPSc), converted from normal prion protein (PrPC), causes prion disease. Although prion disease has been reported in several mammalian species, chickens are known to show strong resistance to prion diseases. In addition to chickens, the domestic duck occupies a large proportion in the poultry industry and may be regarded as a potential resistant host against prion disease. However, the DNA sequence of the prion protein gene (PRNP) has not been reported in domestic ducks. Here, we performed amplicon sequencing targeting the duck PRNP gene with the genomic DNA of Pekin ducks. In addition, we aligned the PrP sequence of the Pekin duck with that of various species using ClustalW2 and carried out phylogenetic analysis using Molecular Evolutionary Genetics Analysis X (MEGA X). We also constructed the structural modeling of the tertiary and secondary structures in avian PrP using SWISS-MODEL. Last, we investigated the aggregation propensity on Pekin duck PrP using AMYCO. We first reported the DNA sequence of the PRNP gene in Pekin ducks and found that the PrP sequence of Pekin ducks is more similar to that of geese than to that of chickens and mallards (wild ducks). Interestingly, Pekin duck PrP showed a high proportion of β-sheets compared to that of chicken PrP, and a high aggregation propensity compared to that of avian PrPs. However, Pekin duck PrP with substitutions of chicken-specific amino acids showed reduced aggregation propensities. To the best of our knowledge, this is the first report on the genetic characteristics of the PRNP sequence in Pekin ducks.

Prion protein gene analysis in new variant cases of Creutzfeldt-Jakob disease

The Lancet ◽  
1996 ◽  
Vol 348 (9019) ◽  
pp. 56 ◽  
Author(s):  
John Collinge ◽  
Jonathan Beck ◽  
Tracy Campbell ◽  
Kathy Estibeiro ◽  
Robert G Will
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Gene Analysis ◽  
Prion Protein Gene ◽  
New Variant ◽  
Jakob Disease

scholarly journals A case of Creutzfeldt-Jakob disease with E200K mutation presenting with hearing loss and central hypoventilation

2018 ◽  
Vol 58 (11) ◽  
pp. 673-676 ◽  
Author(s):  
Shinji Miyagawa ◽  
Taiji Mukai ◽  
Hiroshi Yaguchi
Keyword(s):  
Hearing Loss ◽  
E200k Mutation ◽  
Jakob Disease ◽  
Central Hypoventilation

Novel prion protein gene mutation at codon 196 (E196A) in a septuagenarian with Creutzfeldt–Jakob disease

2014 ◽  
Vol 21 (1) ◽  
pp. 175-178 ◽  
Author(s):  
Hongliang Zhang ◽  
Meibo Wang ◽  
Limin Wu ◽  
Haining Zhang ◽  
Tao Jin ◽  
...  
Keyword(s):  
Prion Protein ◽  
Gene Mutation ◽  
Protein Gene ◽  
Prion Protein Gene ◽  
Jakob Disease

Identification of three novel mutations (E196K, V203I, E211Q) in the prion protein gene (PRNP) in inherited prion diseases with Creutzfeldt-Jakob disease phenotype

2000 ◽  
Vol 15 (5) ◽  
pp. 482-482 ◽  
Author(s):  
Katell Peoc'h ◽  
Philippe Manivet ◽  
Patrice Beaudry ◽  
Fran�oise Attane ◽  
G�rard Besson ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Prion Diseases ◽  
Prion Protein Gene ◽  
Disease Phenotype ◽  
Novel Mutations ◽  
Jakob Disease

scholarly journals Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease

2008 ◽  
Vol 363 (1510) ◽  
pp. 3755-3763 ◽  
Author(s):  
Sebastian Brandner ◽  
Jerome Whitfield ◽  
Ken Boone ◽  
Anderson Puwa ◽  
Catherine O'Malley ◽  
...  
Keyword(s):  
Prion Protein ◽  
Human Prion Disease ◽  
Peripheral Tissues ◽  
Prion Strain ◽  
Pathological Analysis ◽  
Lymphoreticular Tissue ◽  
Jakob Disease ◽  
Strain Type ◽  
Few Data ◽  
The Brain

While the neuropathology of kuru is well defined, there are few data concerning the distribution of disease-related prion protein in peripheral tissues. Here we report the investigation of brain and peripheral tissues from a kuru patient who died in 2003. Neuropathological findings were compared with those seen in classical (sporadic and iatrogenic) Creutzfeldt–Jakob disease (CJD) and variant CJD (vCJD). The neuropathological findings of the kuru patient showed all the stereotypical changes that define kuru, with the occurrence of prominent PrP plaques throughout the brain. Lymphoreticular tissue showed no evidence of prion colonization, suggesting that the peripheral pathogenesis of kuru is similar to that seen in classical CJD rather than vCJD. These findings now strongly suggest that the characteristic peripheral pathogenesis of vCJD is determined by prion strain type alone rather than route of infection.

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