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

Choi BY, Kim SY, Seo SY, An SS, Kim S, Park SE, Lee SH, Choi YJ, Kim SJ, Kim CK, Park JS, Ju YR - BMC Infect. Dis. (2009)

Bottom Line: The 58-year-old patient with the E200K mutation coupled to the 129MV codon had gait disturbance, dysarthria, agitation, and ataxic gait, and progressed rapidly to death 3 months from the first onset of symptoms.The 65-year-old patient with the M232R mutation showed rapidly progressive memory decline and gait disturbance, and died within 16 months after onset of symptoms.Despite differences in ethnicity, the clinical and pathological outcomes were similar to the respective mutations around the world, except absence of insomnia in D178N-129M subject.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Arboviruses, Center for Immunology and Pathology, National Institute of Health, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea. choiby@cdc.go.kr

ABSTRACT

Background: Polymorphisms of the human prion protein gene (PRNP) contribute to the genetic determinants of Creutzfeldt-Jakob disease (CJD). Numerous polymorphisms in the promoter regions as well as the open reading frame of PRNP were investigated. Greater than 90% of Korean, Chinese, and Japanese carry the homozygote 129 MM codon. In Korea, polymorphisms have not been comprehensively studied, except codons 129 and 219 in PRNP among Korean CJD cases. Although polymorphisms at codons 129 and 219 play an important role in susceptibility to sporadic CJD, patients with other polymorphisms in PRNP exhibited critical distinctions of clinical symptoms.

Methods: The genetic analyses of PRNP were carried out among probable CJD patients in comparison with the results from magnetic resonance imaging (MRI) and electroencephalogram (EEG).

Results: The molecular analyses revealed that three mutations at codons D178N, E200K, and M232R in heterozygosity. Patients with the D178N and M232R mutations had a 129MM codon, whereas the patient with the E200K mutation showed 129MV heterozygosity. They all revealed strong 14-3-3 positive signals. The 67-year-old patient with the D178N-129M mutation showed progressive gait disturbance and dysarthria was in progress. The 58-year-old patient with the E200K mutation coupled to the 129MV codon had gait disturbance, dysarthria, agitation, and ataxic gait, and progressed rapidly to death 3 months from the first onset of symptoms. The 65-year-old patient with the M232R mutation showed rapidly progressive memory decline and gait disturbance, and died within 16 months after onset of symptoms.

Conclusion: Despite differences in ethnicity, the clinical and pathological outcomes were similar to the respective mutations around the world, except absence of insomnia in D178N-129M subject.

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Increased 14-3-3 was observed in CSF from probable CJD patients using immunoblot. CSF from healthy control and probable CJD patients were compared with 293T cell transfected with the pEF6/V5-His plasmid encoding 14-3-3β, and the CSF of a definite sCJD patient as positive control.
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Figure 1: Increased 14-3-3 was observed in CSF from probable CJD patients using immunoblot. CSF from healthy control and probable CJD patients were compared with 293T cell transfected with the pEF6/V5-His plasmid encoding 14-3-3β, and the CSF of a definite sCJD patient as positive control.

Mentions: In the Western blot of the 14-3-3 protein, band from the 293T cells transfected with 14-3-3β expression plasmid matched exactly the bands from the CSF of the positive control and probable CJD patients, confirming the bands from probable CJD patients as 14-3-3. The 14-3-3 appeared to have slight signal in the CSF of negative control, which was obtained from a patient with Japanese encephalitis virus (JEV). Later, this patient was diagnosed as normal. The detected levels of 14-3-3 in CSF from Cases 1, 2, and 3 were similar, although mutated codons in PRNP were different (Figure 1).


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

Choi BY, Kim SY, Seo SY, An SS, Kim S, Park SE, Lee SH, Choi YJ, Kim SJ, Kim CK, Park JS, Ju YR - BMC Infect. Dis. (2009)

Increased 14-3-3 was observed in CSF from probable CJD patients using immunoblot. CSF from healthy control and probable CJD patients were compared with 293T cell transfected with the pEF6/V5-His plasmid encoding 14-3-3β, and the CSF of a definite sCJD patient as positive control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2749045&req=5

Figure 1: Increased 14-3-3 was observed in CSF from probable CJD patients using immunoblot. CSF from healthy control and probable CJD patients were compared with 293T cell transfected with the pEF6/V5-His plasmid encoding 14-3-3β, and the CSF of a definite sCJD patient as positive control.
Mentions: In the Western blot of the 14-3-3 protein, band from the 293T cells transfected with 14-3-3β expression plasmid matched exactly the bands from the CSF of the positive control and probable CJD patients, confirming the bands from probable CJD patients as 14-3-3. The 14-3-3 appeared to have slight signal in the CSF of negative control, which was obtained from a patient with Japanese encephalitis virus (JEV). Later, this patient was diagnosed as normal. The detected levels of 14-3-3 in CSF from Cases 1, 2, and 3 were similar, although mutated codons in PRNP were different (Figure 1).

Bottom Line: The 58-year-old patient with the E200K mutation coupled to the 129MV codon had gait disturbance, dysarthria, agitation, and ataxic gait, and progressed rapidly to death 3 months from the first onset of symptoms.The 65-year-old patient with the M232R mutation showed rapidly progressive memory decline and gait disturbance, and died within 16 months after onset of symptoms.Despite differences in ethnicity, the clinical and pathological outcomes were similar to the respective mutations around the world, except absence of insomnia in D178N-129M subject.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Arboviruses, Center for Immunology and Pathology, National Institute of Health, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea. choiby@cdc.go.kr

ABSTRACT

Background: Polymorphisms of the human prion protein gene (PRNP) contribute to the genetic determinants of Creutzfeldt-Jakob disease (CJD). Numerous polymorphisms in the promoter regions as well as the open reading frame of PRNP were investigated. Greater than 90% of Korean, Chinese, and Japanese carry the homozygote 129 MM codon. In Korea, polymorphisms have not been comprehensively studied, except codons 129 and 219 in PRNP among Korean CJD cases. Although polymorphisms at codons 129 and 219 play an important role in susceptibility to sporadic CJD, patients with other polymorphisms in PRNP exhibited critical distinctions of clinical symptoms.

Methods: The genetic analyses of PRNP were carried out among probable CJD patients in comparison with the results from magnetic resonance imaging (MRI) and electroencephalogram (EEG).

Results: The molecular analyses revealed that three mutations at codons D178N, E200K, and M232R in heterozygosity. Patients with the D178N and M232R mutations had a 129MM codon, whereas the patient with the E200K mutation showed 129MV heterozygosity. They all revealed strong 14-3-3 positive signals. The 67-year-old patient with the D178N-129M mutation showed progressive gait disturbance and dysarthria was in progress. The 58-year-old patient with the E200K mutation coupled to the 129MV codon had gait disturbance, dysarthria, agitation, and ataxic gait, and progressed rapidly to death 3 months from the first onset of symptoms. The 65-year-old patient with the M232R mutation showed rapidly progressive memory decline and gait disturbance, and died within 16 months after onset of symptoms.

Conclusion: Despite differences in ethnicity, the clinical and pathological outcomes were similar to the respective mutations around the world, except absence of insomnia in D178N-129M subject.

Show MeSH
Related in: MedlinePlus