Dataset Information

Characteristics of Chinese patients with genetic CJD who have E196A or E196K mutation in PRNP: comparative analysis of patients identified in the Chinese National CJD Surveillance System

ABSTRACT:

Objective

Two different mutations at codon 196, namely E196A and E196K, have been reported to be related to genetic Creutzfeldt-Jakob disease (CJD). We aimed to comparatively analyse the features of Chinese patients with these two mutations from the CJD surveillance system in China.

Design and setting

Comparative analysis of patients identified via the Chinese National CJD Surveillance System during the period 2006–2020.

Participants

16 Chinese patients with genetic CJD with E196A mutation and 5 with E196K mutation.

Methods

Neurological examination, EEG and MRI, western blot, gene sequence, and RT-QuIC.

Results

The age of onset of E196K genetic CJD cases (median of 61 years) was older than the E196A cases (median of 67 years). Generally, these two subtypes of genetic CJD were more like sporadic Creutzfeldt-Jakob disease (sCJD) clinically. The E196A cases showed more major symptoms, while those of E196K cases were restricted to dementia and mental problems. During progression, more sCJD-associated symptoms and signs gradually appeared, but none of the E196K cases showed cerebellum and visual disturbances. Typical periodic sharp wave complexes on MRI were recorded in 25% of E196A cases but not in E196K cases. sCJD-associated abnormalities on MRI, positive cerebrospinal fluid (CSF) 14-3-3 and increased CSF total tau were observed frequently, ranging from two out of three cases to four out of five cases, without a difference. Positive CSF RT-QuIC was detected in 37.5% (6 of 16) of E196A cases and 60% (3 of 5) of E196K cases. The duration of survival of E196K cases (median of 4.5 months) was shorter than the E196A cases (median of 6.5 months). Moreover, female cases and cases with young age of onset (<60 years) in E196A displayed longer survival time than male patients and cases with older age of onset (≥60 years).

Conclusions

This is the largest comprehensive report of genetic CJD with mutations at codon 196 to date, describing the similarity and diversity in clinical and laboratory tests between patients with E196A and with E196K mutations.

SUBMITTER: Shi Q

PROVIDER: S-EPMC8593757 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.