Mutations at codons 178, 200-129, and 232 contributed to the inherited prion diseases in Korean patients

Bo, Choi; Kim, Su Yeon; Seo, So Young; An, Seong Soo A.; Kim, SangYun; Park, Sang Eun; Lee, Seung-Han; Choi, Yun Ju; Kim, Sang Jin; Kim, Chi Kyeong; Park, Jun-Sun; Ju, Young Ran

doi:10.1186/1471-2334-9-132

Cited by 34 publications

(15 citation statements)

References 28 publications

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“…Among all patients with gPrDs, those with V180I typically are the oldest at disease onset, have the fewest cerebellar symptoms, and show a characteristic pattern of lesions on MRI [27]. Although a few patients with V180I [28] or M232R [29], [30] mutations have been reported from Korea [26], [27] and China [28], long-term nationwide surveillance in Asia has been attempted only in Japan and Taiwan; therefore, further accumulation of cases is needed before ethnic variability can be discussed. Controversy regarding whether the M232R mutation actually causes gPrD remains, not only because patients with this mutation have no family history of the disease, but also because this amino acid substitution has been discovered in a few patients with dementia with Lewy bodies as well as several healthy individuals [31].…”

Section: Discussionmentioning

confidence: 99%

Relationships between Clinicopathological Features and Cerebrospinal Fluid Biomarkers in Japanese Patients with Genetic Prion Diseases

et al. 2013

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A national system for surveillance of prion diseases (PrDs) was established in Japan in April 1999. Here, we analyzed the relationships among prion protein gene (PRNP) mutations and the clinical features, cerebrospinal fluid (CSF) markers, and pathological characteristics of the major genotypes of genetic PrDs (gPrDs). We retrospectively analyzed age at onset and disease duration; the concentrations and incidences of 14-3-3 protein, tau protein, and abnormal prion protein (PrPSc) in the CSF of 309 gPrD patients with P102L, P105L, E200K, V180I, or M232R mutations; and brain pathology in 32 autopsied patients. Three clinical phenotypes were seen: rapidly progressive Creutzfeldt-Jakob disease (CJD), which included 100% of E200K cases, 70% of M232R, and 21% of P102L; slowly progressive CJD, which included 100% of V180I and 30% of M232R; and Gerstmann-Sträussler-Scheinker disease, which included 100% of P105L and 79% of P102L. PrPSc was detected in the CSF of more than 80% of patients with E200K, M232R, or P102L mutations but in only 39% of patients with V180I. V180I was accompanied by weak PrP immunoreactivity in the brain. Patients negative for PrPSc in the CSF were older at disease onset than positive patients. Patients with mutations associated with high 14-3-3 protein levels in the CSF typically had synaptic deposition of PrP in the brain and a rapid course of disease. The presence of small PrP protein fragments in brain homogenates was not correlated with other clinicopathological features. Positivity for PrPSc in the CSF may reflect the pathological process before or at disease onset, or abnormality in the secretion or metabolism of PrPSc. The amount of 14-3-3 protein in the CSF likely indicates the severity of the pathological process and accompanying neuronal damage. These characteristic features of the CSF in cases of gPrD will likely facilitate accurate diagnosis and clinicopathological study of the various disease subtypes.

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Section: Discussionmentioning

confidence: 99%

Relationships between Clinicopathological Features and Cerebrospinal Fluid Biomarkers in Japanese Patients with Genetic Prion Diseases

et al. 2013

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“…In these studies, all Korean sCJD patients were homozygotes for codon 129 M/M and 219 E/E, and their polymorphisms frequencies were similar to those of a previous study of the Japanese population. 19 178D/N, 200E/K and 232M/R were found in probable sCJD patients, 20 and 102P/L was found in one definite GSS patient in Korea. 21 The promoter region SNPs have been identified and studied, but the SNPs in the promoter region associated with prion diseases have not been found in Korea.…”

Section: Resultsmentioning

confidence: 89%

Genotype patterns and characteristics of PRNP in the Korean population

Lee

Choi

et al. 2012

Prion

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Creutzfeldt-Jakob disease (CJD), included in the human transmissible spongiform encephalopathies (TSE), is widely known to be caused by an abnormal accumulation of misfolding prion protein in the brain. Human prion protein gene (PRNP) is mapped in chromosome 20p13 and many single nucleotide polymorphisms (SNPs) in PRNP have been discovered. However, the functionality of SNPs in PRNP is yet unclear, though several SNPs have been known as important mutation related with susceptibility human prion diseases. Our aim is to identify specific genotype patterns and characteristics in the PRNP genomic region and to understand susceptibility among Korean discriminated prion disease patients, suspected CJD patients and the KARE data group. Here, we have researched genotypes and SNPs allele frequencies in PRNP in discriminated prion disease patients group (n = 22), suspected prion diseases patients group (n = 163) and the Korea Association REsource (KARE) data group (n = 296) in Korea. The sequencing regions were promoter region, exon1 and exon2 with their junction parts among 481 samples. A total of 25 SNPs were shown in this study. Nucleotide frequencies of all SNPs are exceedingly tended to bias toward dominant homozygote types except in rs2756271. Genotype frequencies at codon 129 and 219 coding region were similar with previous studies in Korea and Japan. Pathogenic mutations such as 102P/L, 200E/K and 203V/I were observed in discriminated CJD patients group, and 180V/I and 232M/R were shown in suspected prion disease patients group and the KARE data group. A total of 10 SNPs were newly identified, six in the promoter region, one in exon 2 and three in the 3' UTR. The strong and unique linkage disequilibrium (D' = 0.94, r (2) = 0.89) was observed between rs57633656 and rs1800014 which is located in codon 219 coding region. We expect that these data can be provided to determine specific susceptibility and a protective factor of prion diseases not only in Koreans but also in East Asians.

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“…D178N-129M/M dementia cases without insomnia had also been reported in western populations 15. Two D178N cases with 129M/M reported in Korea and Japan had a CJD phenotype or cerebellar ataxia without insomnia 16,17. As mentioned earlier, M/M homozygotes of the codon 129 polymorphism in China was over 95% in general, which was much higher than that in western populations.…”

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confidence: 68%