Dataset Information

The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD).

ABSTRACT: BACKGROUND: Although polymorphisms of PRNP, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s) modulating susceptibility to prion disease. Ribosomal protein SA (RPSA), also called 37 kDa laminin receptor precursor (LRP)/67 kDa laminin receptor (LR), acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR. METHODS: To identify other susceptibility genes involved in prion disease, we performed genetic analysis of RPSA. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD) patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on RPSA by direct sequencing or restriction fragment length polymorphism (RFLP) analysis. RESULTS: We observed four single nucleotide polymorphisms (SNPs), including -8T>C (rs1803893) in the 5'-untranslated region (UTR) of exon 2, 134-32C>T (rs3772138) in the intron, 519G>A (rs2269350) in the intron and 793+58C>T (rs2723) in the intron on the RPSA. The 519G>A (at codon 173) is located in the direct PrP binding site. The genotypes and allele frequencies of the RPSA polymorphisms showed no significant differences between the controls and sporadic CJD patients. CONCLUSION: These results suggest that these RPSA polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of RPSA gene with sporadic CJD.

SUBMITTER: Yun J

PROVIDER: S-EPMC3171711 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD).

Yun Jisuk J Jin Hyoung-Tae HT Lee Yun-Jung YJ Choi Eun-Kyoung EK Carp Richard I RI Jeong Byung-Hoon BH Kim Yong-Sun YS

BMC medical genetics 20110813

<h4>Background</h4>Although polymorphisms of PRNP, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s) modulating susceptibility to prion disease. Ribosomal protein SA (RPSA), also called 37 kDa laminin receptor precursor (LRP)/67 kDa laminin receptor (LR), acts as a receptor for laminin, viruses and prion prot ...[more]

PMID: 21838916

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Project description:BackgroundCreutzfeldt-Jakob Disease (CJD) is the most common prion disease in humans causing a rapidly progressive neurological decline and dementia and is invariably fatal. The familial forms (genetic CJD, gCJD) are caused by mutations in the PRNP gene encoding for the prion protein (PrP). In Israel, there is a large cluster of gCJD cases, carriers of an E200K mutation in the PRNP gene, and therefore the largest population of at-risk individuals in the world. The mutation is not necessarily sufficient for the formation and accumulation of the pathological prion protein (PrPsc), suggesting that other, genetic and non-genetic factors affect the age at symptoms onset. Here we present the protocol of a cross-sectional and longitudinal natural history study of gCJD patients and first-degree relatives of gCJD patients, aiming to identify biological markers of preclinical CJD and risk factors for phenoconversion.MethodsThe study has two groups: Patients diagnosed with gCJD, and first-degree healthy relatives (HR) (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD. At baseline, and at the end of every year, healthy participants are invited for an "in-depth" visit, which includes a clinical evaluation, blood and urine collection, gait assessment, brain MRI, lumbar puncture (LP), and Polysomnography (PSG). At 6 months from baseline, and then halfway through each year, participants are invited for a "brief" visit, which includes a clinical evaluation, short cognitive assessment, and blood and urine collection. gCJD patients will be invited for one "in-depth" visit, similar to the baseline visit of healthy relatives.DiscussionThis continuous follow-up of the participants and the frequent assessments will allow early identification and diagnosis in case of conversion into disease. The knowledge generated from this study is likely to advance the understanding of the underlying clinicopathological processes that occur at the very beginning of CJD, as well as potential genetic and environmental risk factors for the development of the disease, therefore advancing the development of safe and efficient interventions.Trial registrationThe study is an observational study. It has registered retrospectively in https://clinicaltrials.gov/ and has been assigned an identification number NCT05746715.

Project description:BackgroundCreutzfeldt-Jakob disease (CJD) is a rare, fatal, neurodegenerative prion disease potentially transmissible through corneal transplantation. While statistical analyses performed two decades ago estimated the overall prevalence of CJD in the corneal donor pool to be low, the recent significant increase in corneal transplants performed and deaths due to CJD in the U.S. warrants a contemporary risk analysis.MethodsA literature review was conducted to determine the overall number of globally reported cases of CJD transmission through corneal transplantation. U.S. mortality and cornea donation data were utilized to estimate the age-stratified prevalence of undiagnosed, latent CJD in the cornea donor pool in 2018. A historical statistical analysis was performed to estimate the number of corneas from donors with latent CJD entering the U.S. donor pool for each year between 1979 and 2018. From these statistical analyses, risk factors of iatrogenic transmission were identified and summarized.ResultsTen reported cases of iatrogenic transmission of CJD through corneal transplants were identified globally. In 2018, an estimated 3.8 corneas from donors with undiagnosed latent CJD potentially entered the pool of 111,703 transplant-intended corneas harvested from individuals aged 31-80. Between 1979 and 2018, an estimated 47 corneas may have entered the U.S. transplant-intended pool from donors with latent CJD aged 35 to 84. The advanced age of donors and a history of multiple transplants in recipients were both prominent risk factors for iatrogenic transmission.ConclusionsThe 10 reported global cases of iatrogenic transmission likely under-represent the number of individuals with a coinciding history of death by CJD and prior corneal transplantation, as supported by our statistical analysis and lack of geographical diversity of reported cases. As effective screening methods develop and globalization of cornea transplantation broadens, it is of utmost importance that cornea transplantation history among victims of CJD should be investigated and reported.

Dataset Information

The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD).

Publications

The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD).

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