Related Experiment Video
Updated: May 16, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
PRRT2 c.649dupC mutation derived from de novo in paroxysmal kinesigenic dyskinesia
Hong-Fu Li1, Wang Ni, Zhi-Qi Xiong
1Department of Neurology, Huashan Hospital, Institutes of Brain Science, Shanghai Medical College, Fudan University, China.
Aims:
PRRT2 was recently identified as a causative gene for paroxysmal kinesigenic dyskinesia (PKD), and the c.649dupC mutation was shown to be a "high frequency" mutation. This mutation was also identified in many sporadic cases. This might be attributed to the incomplete penetrance of c.649dupC. Alternatively, c.649dupC might derive from de novo. The aim of this study is to elucidate the possibility concerning de novo mutagenesis of PRRT2 mutations in PKD.
Methods:
Nine sporadic Chinese PKD patients including one Mongolian patient were recruited. Direct sequencing of PRRT2 was performed in them and their parents. Haplotype analysis was conducted to confirm the biological relationship.
Results:
A novel mutation, c.133_136delCCAG, was identified in one Han patient and his unaffected mother. The c.649dupC mutation was detected in another Han patient and his unaffected father. To our interest, c.649dupC was detected in the Mongolian patient but not in his parents. Haplotype analysis confirmed the biological relationship among the trio. No mutations were identified in the remaining six patients.
Conclusion:
These findings demonstrate the heterogeneity of PKD, and the de novo mutagenesis of PRRT2 gene might indicate the genetic instability of this region.
Insights
Genetic analysis of the PRRT2 gene in paroxysmal kinesigenic dyskinesia (PKD) cases suggests de novo mutations may contribute to disease development. This highlights potential genetic instability in the PRRT2 region.
Area of Science:
- Genetics
- Neurology
Background:
- The proline-rich transmembrane protein 2 (PRRT2) gene is a known cause of paroxysmal kinesigenic dyskinesia (PKD).
- The c.649dupC mutation in PRRT2 is frequent in sporadic PKD cases, but incomplete penetrance or de novo origin are possible explanations.
Purpose of the Study:
- To investigate the potential for de novo mutagenesis of PRRT2 mutations in sporadic cases of paroxysmal kinesigenic dyskinesia (PKD).
Main Methods:
- Direct sequencing of the PRRT2 gene in nine sporadic Chinese PKD patients and their parents.
- Haplotype analysis to confirm familial relationships.
Main Results:
- A novel mutation (c.133_136delCCAG) was found in one patient and his unaffected mother.
- The c.649dupC mutation was identified in another patient and his unaffected father, and also in a Mongolian patient whose parents were negative for the mutation.
- No mutations were found in six other patients.
Conclusions:
- The study demonstrates genetic heterogeneity in PKD.
- De novo mutagenesis of the PRRT2 gene is suggested, indicating potential genetic instability in this region.
Related Concept Videos
01:24Parkinson Disease l: Introduction
01:21Huntington Disease l: Introduction
01:24Parkinson Disease ll: Pathophysiology
01:11Alterations in Muscle Tone lll
01:24Parkinson's Disease: Treatment
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of its...
01:15Parkinson's Disease: Overview