Elevated E200K Somatic Mutation of the Prion Protein Gene (<i>PRNP</i>) in the Brain Tissues of Patients with Sporadic Creutzfeldt–Jakob Disease (CJD)
Sporadic Creutzfeldt–Jakob disease (CJD) is a major human prion disease worldwide. CJD is a fatal neurodegenerative disease caused by an abnormal prion protein (PrP<sup>Sc</sup>). To date, the exact etiology of sporadic CJD has not been fully elucidated. We investigated the E200K and V20...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/19/14831 |
| Summary: | Sporadic Creutzfeldt–Jakob disease (CJD) is a major human prion disease worldwide. CJD is a fatal neurodegenerative disease caused by an abnormal prion protein (PrP<sup>Sc</sup>). To date, the exact etiology of sporadic CJD has not been fully elucidated. We investigated the E200K and V203I somatic mutations of the prion protein gene (<i>PRNP</i>) in sporadic CJD patients and matched healthy controls using pyrosequencing. In addition, we estimated the impact of somatic mutations on the human prion protein (PrP) using PolyPhen-2, PANTHER and PROVEAN. Furthermore, we evaluated the 3D structure and electrostatic potential of the human PrP according to somatic mutations using DeepView. The rates of <i>PRNP</i> K200 somatic mutation were significantly increased in the frontal cortex and hippocampus of sporadic CJD patients compared to the matched controls. In addition, the electrostatic potential of the human PrP was significantly changed by the K200 somatic mutation of the <i>PRNP</i> gene. To the best of our knowledge, this is the first report on an association of the <i>PRNP</i> K200 somatic mutation with sporadic CJD. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |